Safety/Efficacy of MEDI-551 in Combination with Immunomodulating Therapies in Subjects with Aggressive B-cell Lymphomas

Study identifier:D2852C00004

ClinicalTrials.gov identifier:NCT02271945

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1b/2 Open-label Study to Evaluate the Safety/Efficacy of MEDI-551 in Combination with Immunomodulating Therapy in Subjects with Relapsed or Refractory Aggressive B-cell Lymphomas

Medical condition

Relapsed/Refractory Aggressive B-cell Lymphomas

Phase

Phase 1/2

Healthy volunteers

Study drug

MEDI-551 12 mg/kg, MEDI0680 2.5 mg/kg, MEDI0680 10 mg/kg

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 01 Dec 2014

Primary Completion Date: 24 May 2016

Study Completion Date: 24 May 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2018 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

• Histologically confirmed aggressive diffuse large B-cell lymphoma (DLBCL), including follicular lymphoma (FL) transforming to DLBCL, transformed indolent lymphoma, mantle cell lymphoma (MCL), or Grade 3B FL for dose-escalation cohorts. Only participants with DLBCL will be enrolled in the dose-expansion cohort.
• Willing to provide a fresh tumor sample
• Evaluable/measurable disease with measurable disease defined as greater than or equal to (>= 1) lesion less than or equal to (<=) 20 mm in one dimension or ≥ 15 mm in 2 dimensions as measured by conventional or high-resolution (spiral) computed tomography (CT). Disease evaluable by the International Working Group criteria (Cheson et al, 2007). (NOTE: Irradiated lesions will not be evaluable.)
• Baseline fludeoxyglucose positron emission tomography (FDG-PET) or FDG-PET/CT scans must show positive lesions compatible with CT-defined anatomical tumor sites.
• Relapsed from or refractory to >= 2 prior chemotherapy regimens with >= 1 regimen containing rituximab or failed 1 prior rituximab-containing regimen and unable to tolerate additional multiagent chemotherapy. NOTE: Subjects enrolled in the dose-escalation portion of the study must have exhausted all available standard therapy.
• At least 100 days past autologous stem cell transplant (ASCT).
• At least 1 year past allogeneic stem-cell transplant (SCT) and off immunosuppression therapy, with no evidence of graft-versus-host disease.
• Eastern Cooperative Oncology Group performance status 0-2.
• Adequate hematological function
• Adequate organ function
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 180 days after the final dose of investigational product.
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1through 90 days after receipt of the final dose of investigational product.

Exclusion Criteria

• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer.
• Receipt of any experimental therapy, mAb, cancer vaccine, chemotherapy or small molecule within 28 days prior to Cycle 1 Day 1 or 5 half-lives of that therapy, whichever is shorter.
• Previous therapy directed against cluster of differentiation 19 (CD19)
• Prior exposure to immunotherapy such as but not limited to other anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), anti-PD 1, or anti-PD-L1 antibodies excluding cancer vaccines.
• Vaccination with a live virus within 28 days prior to receiving the first dose of study drug
• History of other invasive malignancy within 2 years except for cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has been surgically cured.
• Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given unless the subject is clinically stable.
• Human immunodeficiency virus (HIV) positive serology or acquired immunodeficiency syndrome (AIDS).
• Active hepatitis B
• Ongoing >= Grade 2 toxicities from previous cancer therapies or any unresolved > Grade 1 immune-related adverse event (irAE) event unless specifically allowed in the inclusion/exclusion criteria.
• No immunosuppressive therapy within 14 days of Cycle 1 Day 1 of MEDI0680 (AMP-514) dosing.
• Active or prior documented autoimmune or inflammatory disease except vitiligo.
• History of primary immunodeficiency.
• Major surgical procedures (as defined by the principal investigator) within 28 days of Cycle 1 Day 1 or still recovering from prior surgery.
• History of tuberculosis, including those who may have completed prophylactic isoniazid (INH) therapy.
• Documented current central nervous system (CNS) involvement, leptomeningeal disease, or spinal cord compression.
• Pregnancy or lactation.
• Clinically significant abnormality on electrocardiogram (ECG).
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from MEDI-551 or MEDI0680 (AMP-514), or compromise the ability of the subject to give written informed consent.

Location

Research Site

St. Louis, MO, United States, 63110

Location

Research Site

Bronx, NY, United States, 10467

Location

Research Site

Birmingham, AL, United States, 36294-3300

Location

Research Site

Baltimore, MD, United States, 21231

Location

Research Site

Milwaukee, Wisconsin, United States, 53226

Location

Research Site

Cleveland, OH, United States, 44195

Arms	Assigned Interventions
Experimental: MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.	Drug: MEDI-551 12 mg/kg Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 Drug: MEDI0680 2.5 mg/kg Participants will receive IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
Experimental: MEDI-551 12 mg/kg and MEDI0680 10 mg/kg Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.	Drug: MEDI-551 12 mg/kg Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 Drug: MEDI0680 10 mg/kg Participants will receive IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted from 01Dec2014 to 24May2016.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 16 participants were screened in this study. Of which, 6 participants failed screening and 10 participants were enrolled in the study and received the study drugs.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Participant Flow: Overall Study

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
STARTED	5	5
COMPLETED	0	0
NOT COMPLETED	5	5
Death	3	3
Withdrawal by Subject	1	1
Unspecified	1	1

Baseline Characteristics

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

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Baseline Measures

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Total
Number of Participants [units: Participants]	5	5	10
Age Continuous [units: YEARS] Mean ± Standard Deviation	63.2 ± 7.1	63.8 ± 14.8	63.5 ± 11.0
Age, Customized [units: Participants]
< 65 YEARS	3	3	6
>= 65 YEARS	2	2	4
Gender, Male/Female [units: ]
Female	1	2	3
Male	4	3	7
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	1	0	1
Not Hispanic or Latino	4	4	8
Unknown or Not Reported	0	1	1
Race (NIH/OMB) ^[1] [units: ]
American Indian or Alaska Native	0	0	0
Asian	0	1	1
Black or African American	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
White	4	4	8
Unknown or Not Reported	1	0	1
More than one race	0	0	0

Outcome Measures

1. Primary Outcome Measure: Maximum Tolerated Dose (MTD) of MEDI-551 [ Time Frame: Day 1 to Day 28 of Cycle 1 (28-day cycle) ]

Measure Type	Primary
Measure Name	Maximum Tolerated Dose (MTD) of MEDI-551
Measure Description	The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD.
Time Frame	Day 1 to Day 28 of Cycle 1 (28-day cycle)
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.
Evaluable Population for DLT included all participants in the dose escalation portion who received all protocol assigned doses and completed safety follow-up during the first 28-day period of therapy, or experienced a DLT during the DLT evaluation period.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	3	4
Maximum Tolerated Dose (MTD) of MEDI-551 [units: mg/kg]	NA^[1]	NA^[1]

No statistical analysis provided for Maximum Tolerated Dose (MTD) of MEDI-551

2. Primary Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs)
Measure Description	An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	5	5
TESAEs	2	1

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

3. Primary Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities
Measure Description	An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were 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, for the period extending to 90 days after the end of study drug.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities [units: Participants]
Febrile neutropenia	1	0
Hypoglobulinaemia	0	1
Blood alkaline phosphatase increased	0	1
Blood creatinine increased	1	0
Blood pressure increased	1	0
Lymphocyte count decreased	0	2
Neutrophil count decreased	0	1
Platelet count decreased	0	1
White blood cell count decreased	0	1
Hyperglycaemia	0	2
Hyperuricaemia	1	0
Hypocalcaemia	0	1
Hyponatraemia	0	1
Haematuria	1	0
Proteinuria	0	1

No statistical analysis provided for Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities

4. Primary Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Primary
Measure Name	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities
Measure Description	Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were 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, for the period extending to 90 days after the end of study treatment.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities [units: Participants]
Infusion related reaction	1	2
Pyrexia	0	1

No statistical analysis provided for Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities

5. Primary Outcome Measure: Number of Participants With Best Overall Response [ Time Frame: Day 1 to Day 28 of Cycle 13 (28-day cycle) ]

Measure Type	Primary
Measure Name	Number of Participants With Best Overall Response
Measure Description	The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: complete response (disappearance of all evidence of disease), partial response (regression of measurable disease and no new sites), stable disease (SD), progessive disease (PD), and non- evaluable (NE).
Time Frame	Day 1 to Day 28 of Cycle 13 (28-day cycle)
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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Number of Participants With Best Overall Response [units: Participants]
Complete Response	0	1
Partial Response	0	0
Stable Disease	0	1
Progressive Disease	5	3
Non-evaluable	0	0

No statistical analysis provided for Number of Participants With Best Overall Response

6. Secondary Outcome Measure: Mean Peak and Trough Concentrations of MEDI551 [ Time Frame: End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1 ]

Measure Type	Secondary
Measure Name	Mean Peak and Trough Concentrations of MEDI551
Measure Description	The mean peak and Trough concentration of MEDI551 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.
Time Frame	End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Mean Peak and Trough Concentrations of MEDI551 [units: mcg/mL] Mean (Standard Deviation)
Cycle1 Day1 End of Infusion	244 (49.3)	220 (66.2)
C1D8 Predose	103 (13.3)	96.8 (38.3)
C1D8 End of Infusion	329 (63.4)	313 (74.2)
C2D1 Predose	92.4 (36.3)	103 (45.4)
C2D1 End of Infusion	276 (59.1)	336 (76.1)
C3D1 Predose	109 (26.8)	108 (49.9)
C3D1 End of Infusion	325 (71.8)	300 (55.2)
C4D1 Predose	85.7 (NA)^[1]	111 (57.2)
C4D1 End of Infusion	338 (NA)^[1]	292 (77.8)

No statistical analysis provided for Mean Peak and Trough Concentrations of MEDI551

7. Secondary Outcome Measure: Mean Peak and Trough Concentrations of MEDI0680 [ Time Frame: EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1 ]

Measure Type	Secondary
Measure Name	Mean Peak and Trough Concentrations of MEDI0680
Measure Description	The mean peak and Trough concentration of MEDI0680 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.
Time Frame	EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1
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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Mean Peak and Trough Concentrations of MEDI0680 [units: mcg/mL] Mean (Standard Deviation)
C1D2 End of Infusion	49.8 (18.2)	256 (101)
C1D15 Predose	18.7 (2.10)	109 (30.1)
C1D15 End of Infusion	72.5 (12.4)	298 (41.7)
C2D1 Predose	32.8 (6.31)	178 (52.3)
C2D1 End of Infusion	92.9 (17.1)	339 (55.9)
C3D1 Predose	44.1 (3.25)	277 (64.3)
C3D1 End of Infusion	110 (29.6)	590 (NA)^[1]
C4D1 Predose	62.2 (NA)^[1]	364 (77.1)
C4D1 End of Infusion	86.0 (NA)^[1]	595 (NA)^[1]

No statistical analysis provided for Mean Peak and Trough Concentrations of MEDI0680

8. Secondary Outcome Measure: Terminal Half-Life (t1/2) of MEDI551 [ Time Frame: EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1 ]

Measure Type	Secondary
Measure Name	Terminal Half-Life (t1/2) of MEDI551
Measure Description	Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Time Frame	EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Terminal Half-Life (t1/2) of MEDI551 [units: h] Mean (Full Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]

No statistical analysis provided for Terminal Half-Life (t1/2) of MEDI551

9. Secondary Outcome Measure: Terminal Half-Life (t1/2) of MEDI0680 [ Time Frame: EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1 ]

Measure Type	Secondary
Measure Name	Terminal Half-Life (t1/2) of MEDI0680
Measure Description	Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Time Frame	EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1
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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Terminal Half-Life (t1/2) of MEDI0680 [units: h] Median (Full Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]

No statistical analysis provided for Terminal Half-Life (t1/2) of MEDI0680

10. Secondary Outcome Measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680 [ Time Frame: 30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680
Measure Description	A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study.
Time Frame	30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	5	5
Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680 [units: Participants]	1	0

No statistical analysis provided for Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680

11. Secondary Outcome Measure: Duration of Complete Response [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Duration of Complete Response
Measure Description	Duration of Complete Response defined as time from start of first documented Complete Response [CR] to the time of disease progression or death, whichever occurs first. Only participants who have achieved complete response assessed by investigator were evaluated.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	0	0
Duration of Complete Response [units: months]

No statistical analysis provided for Duration of Complete Response

12. Secondary Outcome Measure: Number of Participants with Disease Control [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Number of Participants with Disease Control
Measure Description	Disease control includes CR (disappearance of all evidence of disease), PR (regression of measurable disease and no new sites), or SD for at least 8 weeks.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	0	0
Number of Participants with Disease Control [units: participants]

No statistical analysis provided for Number of Participants with Disease Control

13. Secondary Outcome Measure: Duration of Disease Control [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Duration of Disease Control
Measure Description	Duration of disease control is defined as the time period from the start of disease control event to the event of disease progression.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	0	0
Duration of Disease Control [units: months]

No statistical analysis provided for Duration of Disease Control

14. Secondary Outcome Measure: Progression-free Survival (PFS) [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Progression-free Survival (PFS)
Measure Description	Progression-free survival (PFS) is defined as the time from the start of study drug administration until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	0	0
Progression-free Survival (PFS) [units: months]

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

15. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	Overall survival defined as the time from the start of study drug administration until death due to any cause.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	0	0
Overall Survival (OS) [units: months]

No statistical analysis provided for Overall Survival (OS)

16. Secondary Outcome Measure: Time to Response (TTR) [ Time Frame: From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) ]

Measure Type	Secondary
Measure Name	Time to Response (TTR)
Measure Description	Time to response (TTR) defined as the time from the start of study drug administration until the first documentation of disease response. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR.
Time Frame	From treatment administration to 90-days after last dose of study drug (up to approximately 2 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 were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Measured Values

	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg
Number of Participants Analyzed [units:participants]	0	0
Time to Response (TTR) [units: months]

No statistical analysis provided for Time to Response (TTR)

Serious Adverse Events

Time Frame	From treatment administration to 90 days after last dose of study drug (up to approximately 2 years)
Additional Description	No text entered.

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Serious Adverse Events

MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg

MEDI-551 12 mg/kg and MEDI0680 10 mg/kg

Total, serious adverse events

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

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

Diffuse large b-cell lymphoma recurrent¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Other Adverse Events

Time Frame	From treatment administration to 90 days after last dose of study drug (up to approximately 2 years)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Other Adverse Events

MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg

MEDI-551 12 mg/kg and MEDI0680 10 mg/kg

Total, other (not including serious) adverse events

# participants affected / at risk

5/5 (100.00%)

Blood and lymphatic system disorders

Hypoglobulinaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Eye disorders

Vision blurred¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/5 (40.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

# events

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

1/5 (20.00%)

# events

General disorders and administration site conditions

Chills¹,^†

# participants affected / at risk

1/5 (20.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

2/5 (40.00%)

3/5 (60.00%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Device related infection¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

1/5 (20.00%)

2/5 (40.00%)

# events

Investigations

Blood alkaline phosphatase increased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Investigations

Blood pressure increased¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Investigations

Lymphocyte count decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

# events

Metabolism and nutrition disorders

Hyperuricaemia¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Metabolism and nutrition disorders

Hypocalcaemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Metabolism and nutrition disorders

Vitamin b12 deficiency¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

1/5 (20.00%)

# events

Musculoskeletal and connective tissue disorders

Joint stiffness¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal discomfort¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

# events

Nervous system disorders

Sciatica¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

2/5 (40.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Psychiatric disorders

Stress¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Renal and urinary disorders

Proteinuria¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchiectasis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/5 (0.00%)

2/5 (40.00%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹,^†

# participants affected / at risk

1/5 (20.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary congestion¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Night sweats¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

2/5 (40.00%)

0/5 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

Skin and subcutaneous tissue disorders

Rash papular¹,^†

# participants affected / at risk

1/5 (20.00%)

0/5 (0.00%)

# events

Vascular disorders

Flushing¹,^†

# participants affected / at risk

0/5 (0.00%)

1/5 (20.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

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
No text entered.

Results Point of Contact

Name/Title:	Mohammed Dar
Organization:	MedImmune, LLC
Phone	301-398-4095
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

Investigators

Principal Investigator

MedImmune LLC

Medimmune LLC

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries