A Phase I Study of AZD4635 in Japanese Patients with Advanced Solid Malignancies

Study identifier:D8730C00005

ClinicalTrials.gov identifier:NCT03980821

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD4635 in Japanese Patients with Advanced Solid Malignancies.

Medical condition

Advanced solid malignancies

Phase

Phase 1

Healthy volunteers

Study drug

AZD4635

Sex

All

Actual Enrollment

Study type

Interventional

Age

20 Years - 130 Years

Date

Study Start Date: 04 Jul 2019

Primary Completion Date: 07 Sept 2020

Study Completion Date: 07 Sept 2020

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Other

Verification:

Verified 01 Aug 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Chuo-ku, Japan, 104-0045

Location

Research Site

Kashiwa, Japan, 277-8577

Arms	Assigned Interventions
Experimental: AZD4635 monotherapy Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies	-

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
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Participant Flow: Overall Study

	Cohort 1	Cohort 2
STARTED	3	7
COMPLETED	0	0
NOT COMPLETED	3	7
Withdrawal by Subject	0	1
Condition under investigation worsened	2	6
Subjective disease progression	1	0

Baseline Characteristics

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

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Baseline Measures

	Cohort 1	Cohort 2	Total
Number of Participants [units: Participants]	3	7	10
Age Continuous [units: years] Mean ± Standard Deviation	69.3 ± 7.1	65.6 ± 12.4	66.7 ± 10.8
Age Categorical [units: ]
<=18 years	0	0	0
Between 18 and 65 years	1	4	5
>=65 years	2	3	5
Sex: Female, Male [units: ]
Female	1	0	1
Male	2	7	9
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0	0	0
Asian	3	7	10
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	0	0	0
More than one race	0	0	0
Unknown or Not Reported	0	0	0
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	0	0	0
Not Hispanic or Latino	3	7	10
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: The incidence of Adverse event and SAE [ Time Frame: From the informed consent to 30 days post last dose ]

Measure Type	Primary
Measure Name	The incidence of Adverse event and SAE
Measure Description	Treatment emergent AEs and SAEs occurred after the start of treatment until 30 days post last dose
Time Frame	From the informed consent to 30 days post last dose
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.
Safety analysis set: all patients who received at least one administration of AZD4635

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Measured Values

	Cohort 1	Cohort 2
Number of Participants Analyzed [units:participants]	3	7
The incidence of Adverse event and SAE [units: ]
Number of subjects with any adverse events	2	7
Number of subjects with any SAEs	0	0

No statistical analysis provided for The incidence of Adverse event and SAE

2. Primary Outcome Measure: The incidence of Dose-limiting toxicity (DLTs) [ Time Frame: 25 days (Cycle0 and Cycle1) ]

Measure Type	Primary
Measure Name	The incidence of Dose-limiting toxicity (DLTs)
Measure Description	A DLT is defined as any toxicity not attributable to the disease or disease-related processes under investigation, which occured during DLT assessment period from the first dose of study treatment until assessment prior the planned first dose of Cycle 2. DLTs were reviewed by SRC (Safety Review Committee).
Time Frame	25 days (Cycle0 and Cycle1)
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 analysis set: all patients who completed at least 75% of AZD4635 treatment during Cycles 0 and 1, or all patients who had a DLT during the DLT assessment period

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Measured Values

	Cohort 1	Cohort 2
Number of Participants Analyzed [units:participants]	3	7
The incidence of Dose-limiting toxicity (DLTs) [units: Participants]	0	0

No statistical analysis provided for The incidence of Dose-limiting toxicity (DLTs)

3. Secondary Outcome Measure: Objective response rate (ORR) [ Time Frame: Tumor assessment is Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. ]

Measure Type	Secondary
Measure Name	Objective response rate (ORR)
Measure Description	ORR (objective response rate) assessed by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
Time Frame	Tumor assessment is Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression.
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.
Dosed patients with a baseline tumour assessment or new lesion per RECIST 1.1.

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Measured Values

	Cohort 1	Cohort 2
Number of Participants Analyzed [units:participants]	3	7
Objective response rate (ORR) [units: Participants]	0	0

No statistical analysis provided for Objective response rate (ORR)

4. Secondary Outcome Measure: Maximum plasma concentration (Cmax) [ Time Frame: Samples were collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with Cycle 1 Day 1 until last dose. Expected to be for up to 6 months. ]

Measure Type	Secondary
Measure Name	Maximum plasma concentration (Cmax)
Measure Description	Characterize the single-dose and multiple-dose plasma of AZD4635
Time Frame	Samples were collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with Cycle 1 Day 1 until last dose. Expected to be for up to 6 months.
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 PK analysis set consists of all participants in the safety analysis set who received AZD7442 and who have evaluable serum PK data, with no important protocol deviations thought to impact the analysis of the PK data.

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Measured Values

	Cohort 1	Cohort 2
Number of Participants Analyzed [units:participants]	3	7
Maximum plasma concentration (Cmax) [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Single-dose Cmax	233.9 (29.02%)	378.9 (45.63%)
Multiple-dose Cmax	314.1 (32.09%)	504.6 (66.84%)

No statistical analysis provided for Maximum plasma concentration (Cmax)

5. Secondary Outcome Measure: Disease control rate (DCR) [ Time Frame: Tumor assessment is on Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. Expected to be for up to 6 months. ]

Measure Type	Secondary
Measure Name	Disease control rate (DCR)
Measure Description	DCR at 15 weeks assessed by Response Evaluation Criteria in Solid Tumour version 1 (RECIST v1.1)
Time Frame	Tumor assessment is on Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. Expected to be for up to 6 months.
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.
Dosed patients with a baseline tumour assessment or new lesion per RECIST v1.1

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Measured Values

	Cohort 1	Cohort 2
Number of Participants Analyzed [units:participants]	3	7
Disease control rate (DCR) [units: Participants]	0	0

No statistical analysis provided for Disease control rate (DCR)

6. Secondary Outcome Measure: Area under the plasma concentration-time curve (AUC) [ Time Frame: Samples were collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with cycle 1 Day 1 until last dose. Expected to be for 6 months. ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve (AUC)
Measure Description	Characterize the single-dose and multiple-dose plasma of AZD4635
Time Frame	Samples were collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with cycle 1 Day 1 until last dose. Expected to be for 6 months.
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 PK analysis set consists of all participants in the safety analysis set who received AZD7442 and who have evaluable serum PK data, with no important protocol deviations thought to impact the analysis of the PK data.

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Measured Values

	Cohort 1	Cohort 2
Number of Participants Analyzed [units:participants]	3	7
Area under the plasma concentration-time curve (AUC) [units: ng·h/mL] Geometric Mean (Geometric Coefficient of Variation)
Single-dose AUC (0-24h)	1825 (28.90%)	2926 (30.18%)
Single-dose AUC	2373 (46.67%)	3893 (44.14%)
Multiple-dose AUC (0-24h)	2632 (28.72%)	4216 (47.08%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC)

Serious Adverse Events

Time Frame	Treatment period of unspecified length followed by 30 day follow-up
Additional Description	No text entered.

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD

Serious Adverse Events

	Cohort 1	Cohort 2
Total, serious adverse events
# participants affected / at risk	0/3 (0.00%)	0/7 (0.00%)

Other Adverse Events

Time Frame	Treatment period of unspecified length followed by 30 day follow-up
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
Cohort 1	AZD4635 50 mg QD
Cohort 2	AZD4635 75 mg QD