A Phase 1b Study of MEDI4736 in Combination with Tremelimumab in Subjects with Advanced Non-small Cell Lung Cancer - D4190C00006

Study identifier:D4190C00006

ClinicalTrials.gov identifier:NCT02000947

EudraCT identifier:2015-003715-38

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of MEDI4736 in Combination with Tremelimumab in Subjects with Advanced Non-small Cell Lung Cancer

Medical condition

NSCLC

Phase

Phase 1

Healthy volunteers

Study drug

MEDI4736, Tremelimumab

Sex

All

Actual Enrollment

457

Study type

Interventional

Age

18 Years - 101 Years

Date

Study Start Date: 25 Oct 2013

Primary Completion Date: 17 Sept 2019

Study Completion Date: 17 Sept 2019

Study design

Allocation: N/A
Endpoint Classification: Safety/Efficacy
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2020 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Tampa, FL, United States, 33612

Location

Research Site

New Haven, CT, United States, 06510

Location

Research Site

Los Angeles, CA, United States, 90025

Location

Research Site

New York, NY, United States, 10065

Location

Research Site

Portland, OR, United States, 97213

Location

Research Site

Seattle, WA, United States, 98109

Location

Research Site

New York, NY, United States, 10032

Location

Research Site

Boston, MA, United States, 02215

Arms	Assigned Interventions
Experimental: Total Escalation Participants will receive MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Experimental: Expansion Cohort A Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants will receive IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Experimental: Expansion Cohort B (Co-Adminstration dosing) Immunotherapy-naive participants will receive co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Experimental: Expansion Cohort C (Relapsed) Participants whom disease was relapsed with the previous immunotherapy treatment will receive IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Experimental: Expansion Cohort B (Sequential Adminstration) Immunotherapy-naive participants will receive sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).
Experimental: Expansion Cohort C (Refractory) Participants who were refractory to previous immunotherapy treatment will receive IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb). Drug: Tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (mAb).

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Participant Flow: Overall Study

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
STARTED	102	45	19	213	38	40
COMPLETED	0	1	0	3	0	0
NOT COMPLETED	102	44	19	210	38	40
Withdrawal by Subject	21	15	3	26	6	6
Death	66	24	15	126	28	31
Lost to Follow-up	3	1	0	6	1	1
Unspecified	12	4	1	52	3	2

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Baseline Measures

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)	Total
Number of Participants [units: Participants]	102	45	19	213	38	40	457
Age Continuous [units: Years] Mean ± Standard Deviation	65.3 ± 9.6	68.4 ± 8.3	62.8 ± 10.5	61.2 ± 10.4	66.5 ± 8.2	62.3 ± 8.0	63.4 ± 9.9
Sex: Female, Male [units: ]
Female	47	21	12	80	12	17	189
Male	55	24	7	133	26	23	268
Race/Ethnicity, Customized [units: Participants]
American Indian or Alaskan Native	0	0	0	0	0	0	0
Asian	5	2	0	64	2	3	76
Black or African American	1	1	1	2	1	2	8
Native Hawaiian or Other Pacific Islander	0	0	0	1	0	1	2
White	95	42	17	133	34	30	351
Other (unspecified)	1	0	1	6	1	1	10
Not reported	0	0	0	7	0	3	10
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	3	2	1	12	1	1	20
Not Hispanic or Latino	99	43	17	194	36	37	426
Unknown or Not Reported	0	0	1	7	1	2	11

Outcome Measures

1. Primary Outcome Measure: Number of Participants With Dose-limiting Toxicities (DLT) in the Dose-escalation phase [ Time Frame: From the first dose of MEDI4736 (Day 1) until third dose of MEDI4736 Dose 1 (Day 57) and until second dose of MEDI4736 for other MEDI4736 doses (Day 29) ]

Measure Type	Primary
Measure Name	Number of Participants With Dose-limiting Toxicities (DLT) in the Dose-escalation phase
Measure Description	A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period (From the first dose of MEDI4736 until third dose of MEDI4736 Dose 1 [Day 57] and until second dose of MEDI4736 for other MEDI4736 doses [Day 29]) including any >= Grade 3 colitis, Grade 4 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology), Grade 3 irAE that does not downgrade to <= Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids or downgrade to <= Grade 1 or baseline within 14 days, liver transaminase elevation higher than 8 × upper limit of normal (ULN) or total bilirubin higher than 5 × ULN, any >= Grade 2 pneumonitis that does not resolve to <= Grade 1 within 3 days of the initiation of maximal supportive care.
Time Frame	From the first dose of MEDI4736 (Day 1) until third dose of MEDI4736 Dose 1 (Day 57) and until second dose of MEDI4736 for other MEDI4736 doses (Day 29)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
DLT evaluable population included all participants enrolled in the dose-escalation phase who received the protocol-assigned treatment with MEDI4736 and tremelimumab and completed the safety follow-up through the DLT evaluation period or experienced a DLT or died during the DLT evaluation period.

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.

Measured Values

	Total Escalation
Number of Participants Analyzed [units:participants]	100
Number of Participants With Dose-limiting Toxicities (DLT) in the Dose-escalation phase [units: Participants]	2

No statistical analysis provided for Number of Participants With Dose-limiting Toxicities (DLT) in the Dose-escalation phase

2. Primary Outcome Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Measure Description	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	102	45	19	38	40
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [units: Participants]
Any TEAE	101	44	19	37	38
Any TESAE	68	20	11	26	22

No statistical analysis provided for Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

3. Primary Outcome Measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Measure Description	Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, coagulation, and urine. The data for TEAEs >=5% frequency in any arm are reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	102	45	19	38	40
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [units: Participants]
Anemia	20	5	2	2	7
international normalized ratio increased	1	1	2	0	0
Activated partial thromboplastin time prolonged	0	0	2	1	0
Blood fibrinogen increased	0	0	1	0	0
Alanine aminotransferase increased	13	4	3	0	3
Aspartate aminotransferase increased	11	2	4	0	2
Gamma glutamyl transferase increased	11	1	1	2	1
Blood alkaline phosphatase increased	5	3	3	1	3
Hypoalbuminemia	0	3	2	0	3
Hyperbilirubinemia	0	0	1	1	1
Transaminases increased	0	1	1	0	0
Acute kidney injury	4	3	1	0	1
Blood creatinine increased	11	1	1	2	3
Proteinuria	5	1	1	0	1
Hematuria	0	1	1	0	0
Pollakiuria	0	3	1	0	0
Chromaturia	0	1	1	0	0
Polyuria	0	0	1	0	0
Amylase increased	20	8	1	2	1
Lipase increased	15	6	3	1	4
Hyperglycemia	11	3	2	2	4
Hypomagnesemia	8	2	0	5	2
Hyponatremia	7	5	3	5	4
Hypokalemia	5	5	1	3	7
Hypercalcemia	2	3	0	1	0
Hyperkalemia	2	2	1	1	2
Hypertriglyceridemia	2	0	2	1	2
Hypocalcemia	1	2	1	0	1
Hypoglycemia	0	0	1	1	0
Blood cholesterol increased	0	0	1	0	0
Lymphocyte count decreased	1	1	0	0	2
Blood triglycerides increased	1	0	0	0	3

No statistical analysis provided for Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

4. Primary Outcome Measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES
Measure Description	Number of participants with abnormal vital signs and physical examinations reported as TEAEs are reported. Abnormal vital signs and physical examinations reported as TEAEs included any abnormal findings in body temperature, blood pressure, pulse rate, respiratory rate, and body weight.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	102	45	19	38	40
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES [units: Participants]
Pyrexia	21	4	2	4	2
Hypotension	7	1	3	1	3
Hypoxia	7	2	3	2	3
Hypertension	6	1	0	2	1
Weight decreased	6	4	3	5	5
Heart rate irregular	1	0	0	0	0
Palpitations	1	1	1	0	0
Respiratory distress	0	0	1	0	0

No statistical analysis provided for Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES

5. Primary Outcome Measure: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAES [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAES
Measure Description	Number of participants with abnormal ECG reported as TEAEs are reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	102	45	19	38	40
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAES [units: Participants]
Sinus tachycardia	5	1	0	1	2
Atrial fibrillation	4	3	4	0	0
Sinus bradycardia	2	0	0	0	0
Tachycardia	2	0	0	1	1
Bradycardia	1	0	0	0	0
Electrocardiogram QT prolonged	0	1	0	0	0

No statistical analysis provided for Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAES

6. Primary Outcome Measure: Percentage of Participants With Objective Response (OR) per Blinded Independent Central Review (BICR) in Expansion Cohort B (Sequential Administration) and Cohort C [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Primary
Measure Name	Percentage of Participants With Objective Response (OR) per Blinded Independent Central Review (BICR) in Expansion Cohort B (Sequential Administration) and Cohort C
Measure Description	The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumours (RECIST v1.1). The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days with no evidence of progression in-between.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	213	38	40
Percentage of Participants With Objective Response (OR) per Blinded Independent Central Review (BICR) in Expansion Cohort B (Sequential Administration) and Cohort C [units: Percentage of participants] Number (95% Confidence Interval)	16.9 (12.1 to 22.6)	5.3 (0.6 to 17.7)	0 (0 to 8.8)

No statistical analysis provided for Percentage of Participants With Objective Response (OR) per Blinded Independent Central Review (BICR) in Expansion Cohort B (Sequential Administration) and Cohort C

7. Primary Outcome Measure: Number of Participants With Immune-mediated Treatment-emergent Adverse Events (imTEAEs) and Immune-mediated Treatment-emergent Serious Adverse Events (imTESAEs) for Dose-expansion Cohorts [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Immune-mediated Treatment-emergent Adverse Events (imTEAEs) and Immune-mediated Treatment-emergent Serious Adverse Events (imTESAEs) for Dose-expansion Cohorts
Measure Description	Immune-mediated AEs are defined as any adverse events of special interest (AESI, excluding AESIs of infusion related/ hypersensitivity/ anaphylactic reactions) that required the use of systemic steroids, endocrine therapy, or other immunosuppressants; were consistent with an immune mediated mechanism of action; and no clear alternate etiology. An AESI is one of scientific and medical interest specific event for understanding of the study drugs and may require close monitoring and rapid communication by the investigator to the sponsor.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	45	19	213	38	40
Number of Participants With Immune-mediated Treatment-emergent Adverse Events (imTEAEs) and Immune-mediated Treatment-emergent Serious Adverse Events (imTESAEs) for Dose-expansion Cohorts [units: Participants]
Any imTEAE	13	6	73	9	14
Any imTESAE	4	3	22	4	8

No statistical analysis provided for Number of Participants With Immune-mediated Treatment-emergent Adverse Events (imTEAEs) and Immune-mediated Treatment-emergent Serious Adverse Events (imTESAEs) for Dose-expansion Cohorts

8. Secondary Outcome Measure: Percentage of Participants With OR per Investigator Assessment [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With OR per Investigator Assessment
Measure Description	The OR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days with no evidence of progression in-between.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	102	45	19	213	38	40
Percentage of Participants With OR per Investigator Assessment [units: Percentage of participants] Number (95% Confidence Interval)	16.7 (10.0 to 25.3)	15.6 (6.5 to 29.5)	0 (0 to 17.6)	19.7 (14.6 to 25.7)	7.9 (1.7 to 21.4)	5.0 (0.6 to 16.9)

No statistical analysis provided for Percentage of Participants With OR per Investigator Assessment

9. Secondary Outcome Measure: Duration of Response (DoR) per Investigator Assessment [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Duration of Response (DoR) per Investigator Assessment
Measure Description	The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST V 1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. The DoR per investigator assessment is reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). Duration of response was analyzed for those participants who achieved OR per investigator assessment.

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	17	7	0	42	3	2
Duration of Response (DoR) per Investigator Assessment [units: Weeks] Median (95% Confidence Interval)	126.1 (20.1 to NA) ^[1]	24.4 (14.9 to NA) ^[1]		54.1 (40.3 to NA) ^[1]	23.0 (17.0 to NA) ^[1]	45.8 (24.1 to 67.4)

No statistical analysis provided for Duration of Response (DoR) per Investigator Assessment

10. Secondary Outcome Measure: DoR per BICR [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	DoR per BICR
Measure Description	The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST V 1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. The DoR per BICR is reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). Duration of response was analyzed for those participants who achieved OR per BICR.

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	36	2	0
DoR per BICR [units: Weeks] Median (95% Confidence Interval)	123.0 (53.9 to NA) ^[1]	NA (NA to NA) ^[1]

No statistical analysis provided for DoR per BICR

11. Secondary Outcome Measure: Percentage of Participants with Disease Control (DC) per Investigator Assessment [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Percentage of Participants with Disease Control (DC) per Investigator Assessment
Measure Description	Disease control is defined as a best overall response of confirmed CR, confirmed PR, or stable disease (SD) based on RECIST V 1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The DC per investigator assessment is reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	102	45	19	213	38	40
Percentage of Participants with Disease Control (DC) per Investigator Assessment [units: Percentage of participants] Number (95% Confidence Interval)	47.1 (37.1 to 57.2)	57.8 (42.2 to 72.3)	47.4 (24.4 to 71.1)	54.9 (48.0 to 61.7)	28.9 (15.4 to 45.9)	45.0 (29.3 to 61.5)

No statistical analysis provided for Percentage of Participants with Disease Control (DC) per Investigator Assessment

12. Secondary Outcome Measure: Percentage of participants with DC per BICR [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Percentage of participants with DC per BICR
Measure Description	Disease control is defined as a best overall response of confirmed CR, confirmed PR, or SD based on RECIST V 1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression. The DC per BICR is reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	213	38	40
Percentage of participants with DC per BICR [units: Percentage of participants] Number (95% Confidence Interval)	51.2 (44.3 to 58.1)	28.9 (15.4 to 45.9)	40.0 (24.9 to 56.7)

No statistical analysis provided for Percentage of participants with DC per BICR

13. Secondary Outcome Measure: Progression-free Survival (PFS) per Investigator Assessment [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Progression-free Survival (PFS) per Investigator Assessment
Measure Description	The PFS is defined as the time from the start of study drug until the first documentation of disease progression based on RECIST V 1.1 or death due to any cause, whichever occurred first, regardless of whether the participant withdrew from study treatment or received another anticancer therapy prior to progression. PFS per investigator assessment is reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	80	33	16	181	33	36
Progression-free Survival (PFS) per Investigator Assessment [units: Months] Median (95% Confidence Interval)	2.6 (1.7 to 4.8)	3.5 (1.7 to 7.2)	2.8 (1.6 to 4.7)	3.5 (1.8 to 4.0)	1.7 (1.6 to 1.8)	2.2 (1.6 to 3.5)

No statistical analysis provided for Progression-free Survival (PFS) per Investigator Assessment

14. Secondary Outcome Measure: PFS per BICR [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	PFS per BICR
Measure Description	The PFS is defined as the time from the start of study drug until the first documentation of disease progression based on RECIST V 1.1 or death due to any cause, whichever occurred first, regardless of whether the participant withdrew from study treatment or received another anticancer therapy prior to progression. PFS per BICR is reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	166	31	34
PFS per BICR [units: Months] Median (95% Confidence Interval)	3.5 (1.7 to 3.6)	1.7 (1.6 to 2.6)	2.0 (1.6 to 3.1)

No statistical analysis provided for PFS per BICR

15. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	The OS is defined as the time from the start of study treatment until death due to any cause.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Total Escalation	Expansion Cohort A	Expansion Cohort B (Coadmin)	Expansion Cohort B (Sequential)	Expansion Cohort C (Refractory)	Expansion Cohort C (Relapsed)
Number of Participants Analyzed [units:participants]	66	24	15	126	28	31
Overall Survival (OS) [units: Months] Median (95% Confidence Interval)	14.6 (8.7 to 23.0)	22.1 (14.0 to 29.8)	7.6 (4.4 to 17.9)	14.3 (10.0 to 18.9)	8.3 (6.0 to 10.4)	8.5 (4.0 to 14.3)

No statistical analysis provided for Overall Survival (OS)

16. Secondary Outcome Measure: Number of Participants With TEAEs and TESAEs for Cohort B (Sequential Administration) [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With TEAEs and TESAEs for Cohort B (Sequential Administration)
Measure Description	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)
Number of Participants Analyzed [units:participants]	213
Number of Participants With TEAEs and TESAEs for Cohort B (Sequential Administration) [units: Participants]
Any TEAE	211
Any TESAE	120

No statistical analysis provided for Number of Participants With TEAEs and TESAEs for Cohort B (Sequential Administration)

17. Secondary Outcome Measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohort B (Sequential Administration) [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohort B (Sequential Administration)
Measure Description	Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, coagulation, and urine. The data for TEAEs >=5% frequency in any arm are reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)
Number of Participants Analyzed [units:participants]	213
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohort B (Sequential Administration) [units: Participants]
Anemia	41
Alanine aminotransferase increased	15
Aspartate aminotransferase increased	17
Amylase increased	28
Lipase increased	16
Hyperglycemia	11
Hyponatremia	12
Hypokalemia	11
Hypercalcemia	11

No statistical analysis provided for Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohort B (Sequential Administration)

18. Secondary Outcome Measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohort B (Sequential Administration) [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohort B (Sequential Administration)
Measure Description	Number of participants with abnormal vital signs and physical examinations reported as TEAEs are reported. Abnormal vital signs and physical examinations reported as TEAEs included any abnormal findings in body temperature, blood pressure, pulse rate, respiratory rate, and body weight.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)
Number of Participants Analyzed [units:participants]	213
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohort B (Sequential Administration) [units: Participants]
Pyrexia	33
Hypotension	11
Hypoxia	5
Hypertension	5
Weight decreased	19
Palpitations	1

No statistical analysis provided for Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohort B (Sequential Administration)

19. Secondary Outcome Measure: Number of Participants With Abnormal ECG Reported as TEAES for Cohort B (Sequential Administration) [ Time Frame: From Day 1 through 90 days after the last dose of study drug (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Abnormal ECG Reported as TEAES for Cohort B (Sequential Administration)
Measure Description	Number of participants with abnormal ECG reported as TEAEs are reported.
Time Frame	From Day 1 through 90 days after the last dose of study drug (approximately 6 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab).

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)
Number of Participants Analyzed [units:participants]	213
Number of Participants With Abnormal ECG Reported as TEAES for Cohort B (Sequential Administration) [units: Participants]
Sinus tachycardia	3
Atrial fibrillation	1
Sinus bradycardia	1
Tachycardia	7
Bradycardia	1
Electrocardiogram T wave inversion	2

No statistical analysis provided for Number of Participants With Abnormal ECG Reported as TEAES for Cohort B (Sequential Administration)

20. Secondary Outcome Measure: Maximum Observed Concentration (Cmax) of MEDI4736 After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Maximum Observed Concentration (Cmax) of MEDI4736 After First Dose
Measure Description	The Cmax of MEDI4736 is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of MEDI4736 and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation MEDI4736 Dose 1 (Q4W)	Participants received IV MEDI4736 Dose 1 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 2 (Q4W)	Participants received IV MEDI4736 Dose 2 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 3 (Q4W)	Participants received IV MEDI4736 Dose 3 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation & Expansion MEDI4736 Dose 4 (Q4W)	In escalation part of the study, participants received IV MEDI4736 Dose 4 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months. in expansion part of the study, participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Q4W for up to 4 doses each, followed by IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses for a total duration of 12 months.
Escalation MEDI4736 Dose 2 (Q2W)	Participants received IV MEDI4736 Dose 2 Q2W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.

Measured Values

	Escalation MEDI4736 Dose 1 (Q4W)	Escalation MEDI4736 Dose 2 (Q4W)	Escalation MEDI4736 Dose 3 (Q4W)	Escalation & Expansion MEDI4736 Dose 4 (Q4W)	Escalation MEDI4736 Dose 2 (Q2W)
Number of Participants Analyzed [units:participants]	2	3	35	231	27
Maximum Observed Concentration (Cmax) of MEDI4736 After First Dose [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)	67.3 (14.9%)	259 (19.6%)	296 (33.7%)	409 (45.7%)	224 (23.7%)

No statistical analysis provided for Maximum Observed Concentration (Cmax) of MEDI4736 After First Dose

21. Secondary Outcome Measure: Area Under the Concentration-time Curve From Day 1 to Day 28 (AUC0-28) of MEDI4736 After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Area Under the Concentration-time Curve From Day 1 to Day 28 (AUC0-28) of MEDI4736 After First Dose
Measure Description	The AUC0-28 of MEDI4736 is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of MEDI4736 and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation MEDI4736 Dose 1 (Q4W)	Participants received IV MEDI4736 Dose 1 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 2 (Q4W)	Participants received IV MEDI4736 Dose 2 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 3 (Q4W)	Participants received IV MEDI4736 Dose 3 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation & Expansion MEDI4736 Dose 4 (Q4W)	In escalation part of the study, participants received IV MEDI4736 Dose 4 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months. in expansion part of the study, participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Q4W for up to 4 doses each, followed by IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses for a total duration of 12 months.
Escalation MEDI4736 Dose 2 (Q2W)	Participants received IV MEDI4736 Dose 2 Q2W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.

Measured Values

	Escalation MEDI4736 Dose 1 (Q4W)	Escalation MEDI4736 Dose 2 (Q4W)	Escalation MEDI4736 Dose 3 (Q4W)	Escalation & Expansion MEDI4736 Dose 4 (Q4W)	Escalation MEDI4736 Dose 2 (Q2W)
Number of Participants Analyzed [units:participants]	2	3	28	24	0
Area Under the Concentration-time Curve From Day 1 to Day 28 (AUC0-28) of MEDI4736 After First Dose [units: μg*day/mL] Geometric Mean (Geometric Coefficient of Variation)	639 (7.45%)	2728 (5.06%)	3068 (21.9%)	4209 (33.2%)

No statistical analysis provided for Area Under the Concentration-time Curve From Day 1 to Day 28 (AUC0-28) of MEDI4736 After First Dose

22. Secondary Outcome Measure: Time to Reach Maximum Observed Concentration (Tmax) of MEDI4736 After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Time to Reach Maximum Observed Concentration (Tmax) of MEDI4736 After First Dose
Measure Description	The Tmax of MEDI4736 is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of MEDI4736 and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation MEDI4736 Dose 1 (Q4W)	Participants received IV MEDI4736 Dose 1 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 2 (Q4W)	Participants received IV MEDI4736 Dose 2 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 3 (Q4W)	Participants received IV MEDI4736 Dose 3 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation & Expansion MEDI4736 Dose 4 (Q4W)	In escalation part of the study, participants received IV MEDI4736 Dose 4 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months. in expansion part of the study, participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Q4W for up to 4 doses each, followed by IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses for a total duration of 12 months.
Escalation MEDI4736 Dose 2 (Q2W)	Participants received IV MEDI4736 Dose 2 Q2W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.

Measured Values

	Escalation MEDI4736 Dose 1 (Q4W)	Escalation MEDI4736 Dose 2 (Q4W)	Escalation MEDI4736 Dose 3 (Q4W)	Escalation & Expansion MEDI4736 Dose 4 (Q4W)	Escalation MEDI4736 Dose 2 (Q2W)
Number of Participants Analyzed [units:participants]	2	3	35	231	27
Time to Reach Maximum Observed Concentration (Tmax) of MEDI4736 After First Dose [units: Days] Geometric Mean (Geometric Coefficient of Variation)	0.172 (1.7%)	0.047 (4.3%)	0.048 (11.1%)	0.049 (24.5%)	0.046 (8.70%)

No statistical analysis provided for Time to Reach Maximum Observed Concentration (Tmax) of MEDI4736 After First Dose

23. Secondary Outcome Measure: Trough serum concentration (Ctrough) of MEDI4736 After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Trough serum concentration (Ctrough) of MEDI4736 After First Dose
Measure Description	The Ctrough of MEDI4736 is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q2W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post MEDI4736 infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of MEDI4736 and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation MEDI4736 Dose 1 (Q4W)	Participants received IV MEDI4736 Dose 1 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 2 (Q4W)	Participants received IV MEDI4736 Dose 2 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 3 (Q4W)	Participants received IV MEDI4736 Dose 3 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation & Expansion MEDI4736 Dose 4 (Q4W)	In escalation part of the study, participants received IV MEDI4736 Dose 4 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months. in expansion part of the study, participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Q4W for up to 4 doses each, followed by IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses for a total duration of 12 months.
Escalation MEDI4736 Dose 2 (Q2W)	Participants received IV MEDI4736 Dose 2 Q2W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.

Measured Values

	Escalation MEDI4736 Dose 1 (Q4W)	Escalation MEDI4736 Dose 2 (Q4W)	Escalation MEDI4736 Dose 3 (Q4W)	Escalation & Expansion MEDI4736 Dose 4 (Q4W)	Escalation MEDI4736 Dose 2 (Q2W)
Number of Participants Analyzed [units:participants]	2	5	29	37	0
Trough serum concentration (Ctrough) of MEDI4736 After First Dose [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)	8.72 (29.5%)	36.5 (21.8%)	43.0 (124%)	55.5 (47.7%)

No statistical analysis provided for Trough serum concentration (Ctrough) of MEDI4736 After First Dose

24. Secondary Outcome Measure: Cmax of Tremelimumab After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Cmax of Tremelimumab After First Dose
Measure Description	The Cmax of tremelimumab is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of tremelimumab and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 1 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 2 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 2 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 3 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 3 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Expansion Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 1 Q4W for 4 doses, followed IV MEDI4736 Q4W monotherapy for 12 months in expansion part of the study.

Measured Values

	Escalation Tremelimumab Dose 1 (Q4W)	Escalation Tremelimumab Dose 2 (Q4W)	Escalation Tremelimumab Dose 3 (Q4W)	Expansion Tremelimumab Dose 1 (Q4W)
Number of Participants Analyzed [units:participants]	55	32	9	200
Cmax of Tremelimumab After First Dose [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)	22.5 (36.8%)	57.5 (57.2%)	192 (15.1%)	20.3 (37.0%)

No statistical analysis provided for Cmax of Tremelimumab After First Dose

25. Secondary Outcome Measure: Tmax of Tremelimumab After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Tmax of Tremelimumab After First Dose
Measure Description	The Tmax of tremelimumab is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of tremelimumab and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 1 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 2 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 2 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 3 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 3 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Expansion Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 1 Q4W for 4 doses, followed IV MEDI4736 Q4W monotherapy for 12 months in expansion part of the study.

Measured Values

	Escalation Tremelimumab Dose 1 (Q4W)	Escalation Tremelimumab Dose 2 (Q4W)	Escalation Tremelimumab Dose 3 (Q4W)	Expansion Tremelimumab Dose 1 (Q4W)
Number of Participants Analyzed [units:participants]	55	32	9	200
Tmax of Tremelimumab After First Dose [units: Days] Geometric Mean (Geometric Coefficient of Variation)	0.047 (12.7%)	0.046 (8.81%)	0.047 (11.3%)	0.046 (13.3%)

No statistical analysis provided for Tmax of Tremelimumab After First Dose

26. Secondary Outcome Measure: Ctrough of Tremelimumab After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	Ctrough of Tremelimumab After First Dose
Measure Description	The Ctrough of tremelimumab is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of tremelimumab and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 1 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 2 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 2 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 3 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 3 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Expansion Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 1 Q4W for 4 doses, followed IV MEDI4736 Q4W monotherapy for 12 months in expansion part of the study.

Measured Values

	Escalation Tremelimumab Dose 1 (Q4W)	Escalation Tremelimumab Dose 2 (Q4W)	Escalation Tremelimumab Dose 3 (Q4W)	Expansion Tremelimumab Dose 1 (Q4W)
Number of Participants Analyzed [units:participants]	43	22	6	19
Ctrough of Tremelimumab After First Dose [units: μg/mL] Geometric Mean (Geometric Coefficient of Variation)	2.65 (75.1%)	9.51 (33.6%)	19.5 (122%)	3.26 (59.6%)

No statistical analysis provided for Ctrough of Tremelimumab After First Dose

27. Secondary Outcome Measure: AUC0-28 days of Tremelimumab After First Dose [ Time Frame: Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose) ]

Measure Type	Secondary
Measure Name	AUC0-28 days of Tremelimumab After First Dose
Measure Description	The AUC0-28 days of tremelimumab is reported.
Time Frame	Escalation part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion), Days 8 and 15, and Day 29 (predose); Escalation part (Q4W) and Expansion part (Q4W): Day 1 (predose and 10 minutes post tremelimumab infusion) and Day 29 (predose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic evaluable population included all participants who received at least 1 dose of tremelimumab and had any post-dose PK data point. The “Number of Participants Analyzed” denotes the number of participants evaluated for this outcome measure.

Reporting Groups

	Description
Escalation Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 1 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 2 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 2 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 3 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 3 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Expansion Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 1 Q4W for 4 doses, followed IV MEDI4736 Q4W monotherapy for 12 months in expansion part of the study.

Measured Values

	Escalation Tremelimumab Dose 1 (Q4W)	Escalation Tremelimumab Dose 2 (Q4W)	Escalation Tremelimumab Dose 3 (Q4W)	Expansion Tremelimumab Dose 1 (Q4W)
Number of Participants Analyzed [units:participants]	36	17	9	14
AUC0-28 days of Tremelimumab After First Dose [units: μg*day/mL] Geometric Mean (Geometric Coefficient of Variation)	203 (46.5%)	625 (24.1%)	1800 (25.1%)	239 (33.1%)

No statistical analysis provided for AUC0-28 days of Tremelimumab After First Dose

28. Secondary Outcome Measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 [ Time Frame: Escalation part: Days 1, 29, 85, 141, 169, 253, and 337, end of treatment (EOT), 90 days post EOT, and 6 months post last dose; Expansion part: Days 1, 85, and 169, EOT, 90 days post EOT, and 6 months post last dose (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736
Measure Description	Number of participants with positive ADA titer to MEDI4736 are reported. ADA incidence is defined as either treatment-induced (post baseline ADA-positive only) or treatment-boosted ADA; treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive.
Time Frame	Escalation part: Days 1, 29, 85, 141, 169, 253, and 337, end of treatment (EOT), 90 days post EOT, and 6 months post last dose; Expansion part: Days 1, 85, and 169, EOT, 90 days post EOT, and 6 months post last dose (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ADA evaluable population included all participants who received at least 1 dose of MEDI4736 and had any post-dose ADA data point.

Reporting Groups

	Description
Escalation MEDI4736 Dose 1 (Q4W)	Participants received IV MEDI4736 Dose 1 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 2 (Q4W)	Participants received IV MEDI4736 Dose 2 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation MEDI4736 Dose 3 (Q4W)	Participants received IV MEDI4736 Dose 3 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation & Expansion MEDI4736 Dose 4 (Q4W)	In escalation part of the study, participants received IV MEDI4736 Dose 4 Q4W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months. in expansion part of the study, participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Q4W for up to 4 doses each, followed by IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses for a total duration of 12 months.
Escalation MEDI4736 Dose 2 (Q2W)	Participants received IV MEDI4736 Dose 2 Q2W for 12 months and IV tremelimumab Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.

Measured Values

	Escalation MEDI4736 Dose 1 (Q4W)	Escalation MEDI4736 Dose 2 (Q4W)	Escalation MEDI4736 Dose 3 (Q4W)	Escalation & Expansion MEDI4736 Dose 4 (Q4W)	Escalation MEDI4736 Dose 2 (Q2W)
Number of Participants Analyzed [units:participants]	3	5	35	247	22
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 [units: Participants]
ADA incidence	0	1	4	5	1
Treatment-boosted ADA	0	0	2	0	0
Persistent positive	0	1	4	6	1
Transient positive	0	0	0	0	0

No statistical analysis provided for Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736

29. Secondary Outcome Measure: Number of Participants With Positive ADA to Tremelimumab [ Time Frame: Escalation part: Days 1, 29, 85, 141, 169, 253, and 337, end of treatment (EOT), 90 days post EOT, and 6 months post last dose; Expansion part: Days 1, 85, and 169, EOT, 90 days post EOT, and 6 months post last dose (approximately 6 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive ADA to Tremelimumab
Measure Description	Number of participants with positive ADA titer to tremelimumab are reported. ADA incidence is defined as either treatment-induced (post baseline ADA-positive only) or treatment-boosted ADA; treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive.
Time Frame	Escalation part: Days 1, 29, 85, 141, 169, 253, and 337, end of treatment (EOT), 90 days post EOT, and 6 months post last dose; Expansion part: Days 1, 85, and 169, EOT, 90 days post EOT, and 6 months post last dose (approximately 6 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ADA evaluable population included all participants who received at least 1 dose of tremelimumab and had any post-dose ADA data point.

Reporting Groups

	Description
Escalation Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 1 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 2 (Q4W)	Participants received IV MEDI4736 Q4W/Q2W for 12 months and IV tremelimumab Dose 2 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Escalation Tremelimumab Dose 3 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 3 Q4W for 6 doses and then Q12W for 3 doses (for a total of up to 9 doses) for 12 months in escalation part of the study.
Expansion Tremelimumab Dose 1 (Q4W)	Participants received IV MEDI4736 Q4W and IV tremelimumab Dose 1 Q4W for 4 doses, followed IV MEDI4736 Q4W monotherapy for 12 months in expansion part of the study.

Measured Values

	Escalation Tremelimumab Dose 1 (Q4W)	Escalation Tremelimumab Dose 2 (Q4W)	Escalation Tremelimumab Dose 3 (Q4W)	Expansion Tremelimumab Dose 1 (Q4W)
Number of Participants Analyzed [units:participants]	47	28	9	211
Number of Participants With Positive ADA to Tremelimumab [units: Participants]
ADA incidence	6	1	0	14
Treatment-boosted ADA	0	0	0	0
Persistent positive	3	0	0	8
Transient positive	3	1	0	6

No statistical analysis provided for Number of Participants With Positive ADA to Tremelimumab

30. Secondary Outcome Measure: Number of Participants With Programmed Cell Death Ligand 1 (PD-L1) Disposition in Cohort B (Sequential Administration) [ Time Frame: Screening (Days -28 to -1), Day 50, Day 225 ]

Measure Type	Secondary
Measure Name	Number of Participants With Programmed Cell Death Ligand 1 (PD-L1) Disposition in Cohort B (Sequential Administration)
Measure Description	Number of participants with PD-L1 disposition are reported. It is reported as tumour cells disposition high (>=25%) and low/negative (<25%).
Time Frame	Screening (Days -28 to -1), Day 50, Day 225
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). The “Number of Participants Analyzed” denotes the number of participants for whom a PD-L1 status was obtained.

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)
Number of Participants Analyzed [units:participants]	193
Number of Participants With Programmed Cell Death Ligand 1 (PD-L1) Disposition in Cohort B (Sequential Administration) [units: Participants]
Tumour cells high (TC>=25%)	57
Tumour cells low/negative (TC<25%)	136

No statistical analysis provided for Number of Participants With Programmed Cell Death Ligand 1 (PD-L1) Disposition in Cohort B (Sequential Administration)

31. Secondary Outcome Measure: Cluster of differentiation (CD)8 Cell densities in Cohort B (Sequential Administration) [ Time Frame: Screening (Days -28 to -1), Day 50, Day 225 ]

Measure Type	Secondary
Measure Name	Cluster of differentiation (CD)8 Cell densities in Cohort B (Sequential Administration)
Measure Description	CD8 Cell densities are reported.
Time Frame	Screening (Days -28 to -1), Day 50, Day 225
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
As-treated population included all participants who received any dose of study drugs (MEDI4736 or tremelimumab). The “Number of Participants Analyzed” denotes the number of participants for whom CD8 cell density was obtained.

Reporting Groups

	Description
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.

Measured Values

	Expansion Cohort B (Sequential)
Number of Participants Analyzed [units:participants]	83
Cluster of differentiation (CD)8 Cell densities in Cohort B (Sequential Administration) [units: Cells/mm^2] Mean (Standard Deviation)	357.7 (373.8)

No statistical analysis provided for Cluster of differentiation (CD)8 Cell densities in Cohort B (Sequential Administration)

Serious Adverse Events

Time Frame

From Day 1 through 90 days after the last dose of study drug (approximately 6 years)

Additional Description

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Serious Adverse Events

Total Escalation

Expansion Cohort A

Expansion Cohort B (Coadmin)

Expansion Cohort B (Sequential)

Expansion Cohort C (Refractory)

Expansion Cohort C (Relapsed)

Total, serious adverse events

# participants affected / at risk

68/102 (66.67%)

20/45 (44.44%)

11/19 (57.89%)

120/213 (56.34%)

26/38 (68.42%)

22/40 (55.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

1/40 (2.50%)

# events

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Blood and lymphatic system disorders

Hypocoagulable state¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Blood and lymphatic system disorders

Splenic haemorrhage¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Acute left ventricular failure¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

1/102 (0.98%)

2/45 (4.44%)

4/19 (21.05%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Cardiac tamponade¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Congestive cardiomyopathy¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Myocarditis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Pericardial effusion¹,^†

# participants affected / at risk

2/102 (1.96%)

1/45 (2.22%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Pericarditis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Cardiac disorders

Sinus tachycardia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Endocrine disorders

Addison's disease¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Endocrine disorders

Adrenal insufficiency¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Endocrine disorders

Hyperthyroidism¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Endocrine disorders

Hypophysitis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Endocrine disorders

Hypopituitarism¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Endocrine disorders

Inappropriate antidiuretic hormone secretion¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

3/213 (1.41%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Abdominal mass¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

3/213 (1.41%)

1/38 (2.63%)

1/40 (2.50%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Autoimmune colitis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Colitis¹,^†

# participants affected / at risk

10/102 (9.80%)

4/45 (8.89%)

1/19 (5.26%)

6/213 (2.82%)

1/38 (2.63%)

1/40 (2.50%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

1/102 (0.98%)

2/45 (4.44%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

10/102 (9.80%)

1/45 (2.22%)

0/19 (0.00%)

5/213 (2.35%)

1/38 (2.63%)

3/40 (7.50%)

# events

Gastrointestinal disorders

Enteritis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Enterocolitis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Faecaloma¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Gastrointestinal perforation¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Impaired gastric emptying¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Large intestine perforation¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Lower gastrointestinal haemorrhage¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

3/19 (15.79%)

2/213 (0.94%)

0/38 (0.00%)

1/40 (2.50%)

# events

Gastrointestinal disorders

Oesophageal stenosis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Pneumoperitoneum¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Rectal haemorrhage¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Retroperitoneal haematoma¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/102 (0.00%)

2/45 (4.44%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

2/213 (0.94%)

1/38 (2.63%)

1/40 (2.50%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

4/213 (1.88%)

0/38 (0.00%)

1/40 (2.50%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

4/102 (3.92%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

1/38 (2.63%)

0/40 (0.00%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

4/102 (3.92%)

0/45 (0.00%)

0/19 (0.00%)

3/213 (1.41%)

0/38 (0.00%)

0/40 (0.00%)

# events

General disorders and administration site conditions

Systemic inflammatory response syndrome¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Hepatobiliary disorders

Autoimmune hepatitis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Hepatobiliary disorders

Bile duct obstruction¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Hepatobiliary disorders

Hyperbilirubinaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Infections and infestations

Appendicitis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

0/19 (0.00%)

3/213 (1.41%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Device related infection¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Enterocolitis infectious¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection viral¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Lung infection¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

6/213 (2.82%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

3/102 (2.94%)

0/45 (0.00%)

1/19 (5.26%)

13/213 (6.10%)

7/38 (18.42%)

2/40 (5.00%)

# events

Infections and infestations

Pneumonia haemophilus¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Infections and infestations

Proteus infection¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Infections and infestations

Pyelonephritis acute¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Respiratory syncytial virus infection¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

2/102 (1.96%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

1/38 (2.63%)

0/40 (0.00%)

# events

Infections and infestations

Septic shock¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

3/213 (1.41%)

0/38 (0.00%)

1/40 (2.50%)

# events

Infections and infestations

Soft tissue infection¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Streptococcal sepsis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Tracheobronchitis viral¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Femur fracture¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Hip fracture¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Humerus fracture¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Lumbar vertebral fracture¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Radiation pneumonitis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Radius fracture¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Spinal compression fracture¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Spinal fracture¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

2/19 (10.53%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Amylase increased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Anticoagulation drug level above therapeutic¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

2/19 (10.53%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Lipase increased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Liver function test increased¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Lymphocyte count decreased¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Oxygen saturation decreased¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

5/102 (4.90%)

0/45 (0.00%)

2/19 (10.53%)

4/213 (1.88%)

0/38 (0.00%)

1/40 (2.50%)

# events

Metabolism and nutrition disorders

Hypercalcaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

3/213 (1.41%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

3/102 (2.94%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Hyperuricaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

2/213 (0.94%)

0/38 (0.00%)

1/40 (2.50%)

# events

Metabolism and nutrition disorders

Metabolic acidosis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Type 2 diabetes mellitus¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

1/40 (2.50%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

1/38 (2.63%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myositis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Paraneoplastic arthritis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pathological fracture¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

2/213 (0.94%)

1/38 (2.63%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Polymyositis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Rhabdomyolysis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Spinal stenosis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of colon¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Extradural neoplasm¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

1/38 (2.63%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage iv¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm malignant¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

10/213 (4.69%)

1/38 (2.63%)

2/40 (5.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm progression¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant pleural effusion¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer¹,^†

# participants affected / at risk

11/102 (10.78%)

5/45 (11.11%)

3/19 (15.79%)

47/213 (22.07%)

7/38 (18.42%)

7/40 (17.50%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer metastatic¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

1/38 (2.63%)

1/40 (2.50%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer stage iv¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pericarditis malignant¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of skin¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Brain oedema¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Central nervous system haemorrhage¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Central nervous system lesion¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Cerebral ischaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Depressed level of consciousness¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Dysarthria¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Nervous system disorders

Encephalopathy¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Hydrocephalus¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Intercostal neuralgia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Nervous system disorders

Metabolic encephalopathy¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Nervous system disorders

Myasthenia gravis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Neuromyopathy¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Seizure¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Spinal cord compression¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

0/19 (0.00%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Tension headache¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Nervous system disorders

Tremor¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Vasogenic cerebral oedema¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Product issues

Device malfunction¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Psychiatric disorders

Mental status changes¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/102 (0.98%)

2/45 (4.44%)

1/19 (5.26%)

3/213 (1.41%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Urinary retention¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory distress syndrome¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Aspiration¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial disorder¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial obstruction¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

1/38 (2.63%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

6/102 (5.88%)

1/45 (2.22%)

0/19 (0.00%)

8/213 (3.76%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemothorax¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

3/102 (2.94%)

0/45 (0.00%)

2/19 (10.53%)

3/213 (1.41%)

0/38 (0.00%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

2/19 (10.53%)

6/213 (2.82%)

0/38 (0.00%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Pleuritic pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

5/102 (4.90%)

0/45 (0.00%)

0/19 (0.00%)

4/213 (1.88%)

2/38 (5.26%)

2/40 (5.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

0/102 (0.00%)

2/45 (4.44%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

1/102 (0.98%)

2/45 (4.44%)

3/19 (15.79%)

2/213 (0.94%)

2/38 (5.26%)

3/40 (7.50%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory distress¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

2/102 (1.96%)

1/45 (2.22%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Skin and subcutaneous tissue disorders

Drug reaction with eosinophilia and systemic symptoms¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Skin and subcutaneous tissue disorders

Purpura¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Vascular disorders

Embolism¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Vascular disorders

Vascular compression¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 22.0

Other Adverse Events

Time Frame

From Day 1 through 90 days after the last dose of study drug (approximately 6 years)

Additional Description

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Total Escalation	Participants received MEDI4736 IV escalation doses (Dose 1 or 2 or 3 or 4 ) every 4 weeks (Q4W; up to 13 doses) or every two weeks (Q2W; up to 26 doses) and IV tremelimumab dose (Dose 1, 2, or 3) Q4W for 6 doses and then every 12 weeks (Q12W) for 3 doses (up to 9 doses in total) for 12 months or until disease progression.
Expansion Cohort A	Treatment-naïve, non-epidermal growth factor receptor (non-EGFR) mutation positive, and non-anaplastic lymphoma kinase (non-ALK) rearrangement positive participants received IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Coadmin)	Immunotherapy-naive participants received co-administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort B (Sequential)	Immunotherapy-naive participants received sequential administration of IV MEDI4736 Dose 4 Q4W and IV tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W monotherapy for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Refractory)	Participants who were refractory to previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.
Expansion Cohort C (Relapsed)	Participants whom disease was relapsed with the previous immunotherapy treatment received IV infusion of MEDI4736 Dose 4 Q4W and tremelimumab Dose 1 Q4W for up to 4 doses each, followed by monotherapy with IV MEDI4736 Dose 4 Q4W for 9 doses to complete a total of 12 months of therapy or until disease progression.

Other Adverse Events

Total Escalation

Expansion Cohort A

Expansion Cohort B (Coadmin)

Expansion Cohort B (Sequential)

Expansion Cohort C (Refractory)

Expansion Cohort C (Relapsed)

Total, other (not including serious) adverse events

# participants affected / at risk

96/102 (94.12%)

44/45 (97.78%)

18/19 (94.74%)

205/213 (96.24%)

35/38 (92.11%)

37/40 (92.50%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

20/102 (19.61%)

5/45 (11.11%)

2/19 (10.53%)

40/213 (18.78%)

2/38 (5.26%)

6/40 (15.00%)

# events

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Endocrine disorders

Hyperthyroidism¹,^†

# participants affected / at risk

4/102 (3.92%)

2/45 (4.44%)

2/19 (10.53%)

23/213 (10.80%)

0/38 (0.00%)

1/40 (2.50%)

# events

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

12/102 (11.76%)

1/45 (2.22%)

3/19 (15.79%)

27/213 (12.68%)

4/38 (10.53%)

3/40 (7.50%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

8/102 (7.84%)

3/45 (6.67%)

3/19 (15.79%)

25/213 (11.74%)

3/38 (7.89%)

5/40 (12.50%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

5/102 (4.90%)

0/45 (0.00%)

1/19 (5.26%)

6/213 (2.82%)

1/38 (2.63%)

2/40 (5.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

13/102 (12.75%)

12/45 (26.67%)

4/19 (21.05%)

44/213 (20.66%)

4/38 (10.53%)

12/40 (30.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

42/102 (41.18%)

13/45 (28.89%)

8/19 (42.11%)

49/213 (23.00%)

10/38 (26.32%)

13/40 (32.50%)

# events

Gastrointestinal disorders

Dry mouth¹,^†

# participants affected / at risk

8/102 (7.84%)

6/45 (13.33%)

2/19 (10.53%)

17/213 (7.98%)

1/38 (2.63%)

0/40 (0.00%)

# events

Gastrointestinal disorders

Enterocolitis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

1/40 (2.50%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

27/102 (26.47%)

12/45 (26.67%)

4/19 (21.05%)

39/213 (18.31%)

9/38 (23.68%)

9/40 (22.50%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

1/19 (5.26%)

9/213 (4.23%)

0/38 (0.00%)

1/40 (2.50%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

15/102 (14.71%)

6/45 (13.33%)

2/19 (10.53%)

20/213 (9.39%)

8/38 (21.05%)

8/40 (20.00%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

6/102 (5.88%)

0/45 (0.00%)

2/19 (10.53%)

46/213 (21.60%)

1/38 (2.63%)

3/40 (7.50%)

# events

General disorders and administration site conditions

Chills¹,^†

# participants affected / at risk

5/102 (4.90%)

2/45 (4.44%)

1/19 (5.26%)

8/213 (3.76%)

2/38 (5.26%)

2/40 (5.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

35/102 (34.31%)

15/45 (33.33%)

8/19 (42.11%)

63/213 (29.58%)

14/38 (36.84%)

13/40 (32.50%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

6/102 (5.88%)

0/45 (0.00%)

0/19 (0.00%)

3/213 (1.41%)

0/38 (0.00%)

1/40 (2.50%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

3/213 (1.41%)

0/38 (0.00%)

1/40 (2.50%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

1/102 (0.98%)

4/45 (8.89%)

0/19 (0.00%)

16/213 (7.51%)

2/38 (5.26%)

2/40 (5.00%)

# events

General disorders and administration site conditions

Oedema¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

1/40 (2.50%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

11/102 (10.78%)

11/45 (24.44%)

0/19 (0.00%)

18/213 (8.45%)

2/38 (5.26%)

4/40 (10.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

17/102 (16.67%)

4/45 (8.89%)

2/19 (10.53%)

31/213 (14.55%)

4/38 (10.53%)

2/40 (5.00%)

# events

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Hepatobiliary disorders

Hyperbilirubinaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

1/40 (2.50%)

# events

Immune system disorders

Seasonal allergy¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

0/19 (0.00%)

4/213 (1.88%)

2/38 (5.26%)

0/40 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

3/102 (2.94%)

3/45 (6.67%)

0/19 (0.00%)

3/213 (1.41%)

2/38 (5.26%)

1/40 (2.50%)

# events

Infections and infestations

Candida infection¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

2/19 (10.53%)

0/213 (0.00%)

1/38 (2.63%)

1/40 (2.50%)

# events

Infections and infestations

Lung infection¹,^†

# participants affected / at risk

3/102 (2.94%)

1/45 (2.22%)

1/19 (5.26%)

9/213 (4.23%)

0/38 (0.00%)

2/40 (5.00%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

3/102 (2.94%)

1/45 (2.22%)

1/19 (5.26%)

8/213 (3.76%)

1/38 (2.63%)

0/40 (0.00%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

3/102 (2.94%)

0/45 (0.00%)

1/19 (5.26%)

10/213 (4.69%)

2/38 (5.26%)

1/40 (2.50%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

3/102 (2.94%)

3/45 (6.67%)

0/19 (0.00%)

4/213 (1.88%)

0/38 (0.00%)

1/40 (2.50%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

5/102 (4.90%)

5/45 (11.11%)

1/19 (5.26%)

17/213 (7.98%)

2/38 (5.26%)

3/40 (7.50%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

6/102 (5.88%)

4/45 (8.89%)

0/19 (0.00%)

7/213 (3.29%)

2/38 (5.26%)

1/40 (2.50%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

1/19 (5.26%)

3/213 (1.41%)

1/38 (2.63%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Head injury¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

1/19 (5.26%)

13/213 (6.10%)

0/38 (0.00%)

2/40 (5.00%)

# events

Investigations

Activated partial thromboplastin time prolonged¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

2/19 (10.53%)

3/213 (1.41%)

1/38 (2.63%)

0/40 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

13/102 (12.75%)

4/45 (8.89%)

1/19 (5.26%)

15/213 (7.04%)

0/38 (0.00%)

3/40 (7.50%)

# events

Investigations

Amylase increased¹,^†

# participants affected / at risk

19/102 (18.63%)

8/45 (17.78%)

1/19 (5.26%)

28/213 (13.15%)

2/38 (5.26%)

1/40 (2.50%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

10/102 (9.80%)

2/45 (4.44%)

2/19 (10.53%)

17/213 (7.98%)

0/38 (0.00%)

2/40 (5.00%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

4/102 (3.92%)

3/45 (6.67%)

3/19 (15.79%)

8/213 (3.76%)

1/38 (2.63%)

3/40 (7.50%)

# events

Investigations

Blood cholesterol increased¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

4/213 (1.88%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

11/102 (10.78%)

1/45 (2.22%)

1/19 (5.26%)

8/213 (3.76%)

2/38 (5.26%)

3/40 (7.50%)

# events

Investigations

Blood fibrinogen increased¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Blood thyroid stimulating hormone decreased¹,^†

# participants affected / at risk

6/102 (5.88%)

1/45 (2.22%)

0/19 (0.00%)

7/213 (3.29%)

0/38 (0.00%)

1/40 (2.50%)

# events

Investigations

Blood thyroid stimulating hormone increased¹,^†

# participants affected / at risk

7/102 (6.86%)

1/45 (2.22%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Blood triglycerides increased¹,^†

# participants affected / at risk

1/102 (0.98%)

0/45 (0.00%)

0/19 (0.00%)

1/213 (0.47%)

0/38 (0.00%)

3/40 (7.50%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

10/102 (9.80%)

1/45 (2.22%)

1/19 (5.26%)

10/213 (4.69%)

2/38 (5.26%)

1/40 (2.50%)

# events

Investigations

International normalised ratio increased¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

2/19 (10.53%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Lipase increased¹,^†

# participants affected / at risk

15/102 (14.71%)

6/45 (13.33%)

3/19 (15.79%)

16/213 (7.51%)

1/38 (2.63%)

4/40 (10.00%)

# events

Investigations

Transaminases increased¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

6/102 (5.88%)

4/45 (8.89%)

3/19 (15.79%)

19/213 (8.92%)

5/38 (13.16%)

5/40 (12.50%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

21/102 (20.59%)

10/45 (22.22%)

6/19 (31.58%)

61/213 (28.64%)

8/38 (21.05%)

9/40 (22.50%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

5/102 (4.90%)

1/45 (2.22%)

2/19 (10.53%)

6/213 (2.82%)

3/38 (7.89%)

2/40 (5.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

10/102 (9.80%)

3/45 (6.67%)

2/19 (10.53%)

11/213 (5.16%)

2/38 (5.26%)

4/40 (10.00%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

2/102 (1.96%)

2/45 (4.44%)

1/19 (5.26%)

7/213 (3.29%)

1/38 (2.63%)

2/40 (5.00%)

# events

Metabolism and nutrition disorders

Hypertriglyceridaemia¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

2/19 (10.53%)

7/213 (3.29%)

1/38 (2.63%)

2/40 (5.00%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

3/45 (6.67%)

2/19 (10.53%)

7/213 (3.29%)

0/38 (0.00%)

3/40 (7.50%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

1/102 (0.98%)

2/45 (4.44%)

1/19 (5.26%)

5/213 (2.35%)

0/38 (0.00%)

1/40 (2.50%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

3/213 (1.41%)

1/38 (2.63%)

0/40 (0.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

5/102 (4.90%)

5/45 (11.11%)

1/19 (5.26%)

11/213 (5.16%)

3/38 (7.89%)

7/40 (17.50%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

8/102 (7.84%)

2/45 (4.44%)

0/19 (0.00%)

4/213 (1.88%)

5/38 (13.16%)

2/40 (5.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

7/102 (6.86%)

5/45 (11.11%)

2/19 (10.53%)

11/213 (5.16%)

5/38 (13.16%)

3/40 (7.50%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

13/102 (12.75%)

6/45 (13.33%)

1/19 (5.26%)

36/213 (16.90%)

3/38 (7.89%)

9/40 (22.50%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

10/102 (9.80%)

7/45 (15.56%)

4/19 (21.05%)

31/213 (14.55%)

3/38 (7.89%)

2/40 (5.00%)

# events

Musculoskeletal and connective tissue disorders

Bone pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

7/213 (3.29%)

0/38 (0.00%)

1/40 (2.50%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

9/102 (8.82%)

1/45 (2.22%)

1/19 (5.26%)

4/213 (1.88%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

4/102 (3.92%)

2/45 (4.44%)

1/19 (5.26%)

8/213 (3.76%)

0/38 (0.00%)

1/40 (2.50%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

10/102 (9.80%)

6/45 (13.33%)

0/19 (0.00%)

15/213 (7.04%)

4/38 (10.53%)

5/40 (12.50%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

7/102 (6.86%)

1/45 (2.22%)

0/19 (0.00%)

19/213 (8.92%)

3/38 (7.89%)

1/40 (2.50%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

5/102 (4.90%)

1/45 (2.22%)

1/19 (5.26%)

14/213 (6.57%)

0/38 (0.00%)

1/40 (2.50%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

5/102 (4.90%)

1/45 (2.22%)

2/19 (10.53%)

3/213 (1.41%)

0/38 (0.00%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

7/102 (6.86%)

3/45 (6.67%)

1/19 (5.26%)

9/213 (4.23%)

1/38 (2.63%)

0/40 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in jaw¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour pain¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

0/19 (0.00%)

4/213 (1.88%)

2/38 (5.26%)

1/40 (2.50%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

10/102 (9.80%)

4/45 (8.89%)

0/19 (0.00%)

18/213 (8.45%)

2/38 (5.26%)

5/40 (12.50%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

5/102 (4.90%)

4/45 (8.89%)

0/19 (0.00%)

6/213 (2.82%)

1/38 (2.63%)

1/40 (2.50%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

12/102 (11.76%)

1/45 (2.22%)

1/19 (5.26%)

17/213 (7.98%)

1/38 (2.63%)

3/40 (7.50%)

# events

Nervous system disorders

Peripheral sensory neuropathy¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

2/19 (10.53%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Seizure¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Nervous system disorders

Visual field defect¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

0/40 (0.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

8/102 (7.84%)

3/45 (6.67%)

2/19 (10.53%)

8/213 (3.76%)

3/38 (7.89%)

1/40 (2.50%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

3/102 (2.94%)

0/45 (0.00%)

0/19 (0.00%)

11/213 (5.16%)

3/38 (7.89%)

1/40 (2.50%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

8/102 (7.84%)

5/45 (11.11%)

2/19 (10.53%)

17/213 (7.98%)

4/38 (10.53%)

2/40 (5.00%)

# events

Renal and urinary disorders

Chromaturia¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

1/19 (5.26%)

4/213 (1.88%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Micturition urgency¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

2/19 (10.53%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

1/102 (0.98%)

3/45 (6.67%)

1/19 (5.26%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Polyuria¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Renal and urinary disorders

Proteinuria¹,^†

# participants affected / at risk

5/102 (4.90%)

1/45 (2.22%)

1/19 (5.26%)

1/213 (0.47%)

0/38 (0.00%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

0/102 (0.00%)

1/45 (2.22%)

0/19 (0.00%)

2/213 (0.94%)

2/38 (5.26%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

19/102 (18.63%)

10/45 (22.22%)

4/19 (21.05%)

39/213 (18.31%)

8/38 (21.05%)

7/40 (17.50%)

# events

Respiratory, thoracic and mediastinal disorders

Dry throat¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

0/213 (0.00%)

0/38 (0.00%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

1/19 (5.26%)

2/213 (0.94%)

0/38 (0.00%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

20/102 (19.61%)

18/45 (40.00%)

6/19 (31.58%)

59/213 (27.70%)

10/38 (26.32%)

11/40 (27.50%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹,^†

# participants affected / at risk

2/102 (1.96%)

0/45 (0.00%)

1/19 (5.26%)

8/213 (3.76%)

0/38 (0.00%)

4/40 (10.00%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹,^†

# participants affected / at risk

1/102 (0.98%)

3/45 (6.67%)

0/19 (0.00%)

15/213 (7.04%)

3/38 (7.89%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

4/102 (3.92%)

2/45 (4.44%)

1/19 (5.26%)

3/213 (1.41%)

2/38 (5.26%)

2/40 (5.00%)

# events

Respiratory, thoracic and mediastinal disorders

Laryngeal haemorrhage¹,^†

# participants affected / at risk

0/102 (0.00%)

0/45 (0.00%)

1/19 (5.26%)

2/213 (0.94%)

1/38 (2.63%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

6/102 (5.88%)

5/45 (11.11%)

1/19 (5.26%)

3/213 (1.41%)

2/38 (5.26%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

1/102 (0.98%)

3/45 (6.67%)

0/19 (0.00%)

6/213 (2.82%)

1/38 (2.63%)

0/40 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

0/102 (0.00%)

2/45 (4.44%)

0/19 (0.00%)

9/213 (4.23%)

4/38 (10.53%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

1/102 (0.98%)

3/45 (6.67%)

0/19 (0.00%)

5/213 (2.35%)

1/38 (2.63%)

3/40 (7.50%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

8/102 (7.84%)

5/45 (11.11%)

1/19 (5.26%)

14/213 (6.57%)

5/38 (13.16%)

1/40 (2.50%)

# events

Respiratory, thoracic and mediastinal disorders

Wheezing¹,^†

# participants affected / at risk

2/102 (1.96%)

6/45 (13.33%)

1/19 (5.26%)

4/213 (1.88%)

3/38 (7.89%)

1/40 (2.50%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹,^†

# participants affected / at risk

6/102 (5.88%)

2/45 (4.44%)

1/19 (5.26%)

12/213 (5.63%)

2/38 (5.26%)

1/40 (2.50%)

# events

Skin and subcutaneous tissue disorders

Night sweats¹,^†

# participants affected / at risk

2/102 (1.96%)

3/45 (6.67%)

0/19 (0.00%)

2/213 (0.94%)

1/38 (2.63%)

0/40 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

26/102 (25.49%)

9/45 (20.00%)

0/19 (0.00%)

44/213 (20.66%)

8/38 (21.05%)

5/40 (12.50%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

22/102 (21.57%)

2/45 (4.44%)

1/19 (5.26%)

35/213 (16.43%)

4/38 (10.53%)

2/40 (5.00%)

# events

Skin and subcutaneous tissue disorders

Rash macular¹,^†

# participants affected / at risk

0/102 (0.00%)

3/45 (6.67%)

0/19 (0.00%)

1/213 (0.47%)

1/38 (2.63%)

0/40 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

9/102 (8.82%)

11/45 (24.44%)

1/19 (5.26%)

6/213 (2.82%)

3/38 (7.89%)

1/40 (2.50%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

1/19 (5.26%)

2/213 (0.94%)

0/38 (0.00%)

0/40 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

1/102 (0.98%)

1/45 (2.22%)

1/19 (5.26%)

3/213 (1.41%)

1/38 (2.63%)

0/40 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

6/102 (5.88%)

1/45 (2.22%)

0/19 (0.00%)

5/213 (2.35%)

2/38 (5.26%)

1/40 (2.50%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

5/102 (4.90%)

1/45 (2.22%)

3/19 (15.79%)

11/213 (5.16%)

1/38 (2.63%)

3/40 (7.50%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 22.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Shahram Rahimian
Organization:	MedImmune, LLC
Phone	+1-800-236-9933
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Cancer Study Locator Service

1 877 400 4656

AstraZeneca@emergingmed.com

Investigators

Principal Investigator

MedImmune LLC

MedImmune

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site