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

Study Overview
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Brief Summary
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This is 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. This study consists of 2 cohorts, Cohort1 and Cohort2. At least 3 or up to 6 evaluable Japanese patients with advanced solid malignancies will be enrolled in Cohort1 and 6 evaluable patients will be enrolled in Cohort2.

Detailed Description
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Objectives: Primary objective: Investigate the safety and tolerability of AZD4635 monotherapy in Japanese patients Secondary objective: Characterize the single-dose and multiple-dose plasma pharmacokinetic (PK) parameters of AZD4635 monotherapy Determine the preliminary anti-tumor activity of AZD4645 monotherapy Overall design: This is a phase I, open-label study of AZD4635 in Japanese patients with advanced solid malignancies. The study consists of 2 cohorts, Cohort 1 and Cohort 2. At least 3 or up to 6 evaluable Japanese subjects with advanced solid malignancies will be enrolled in Cohort 1 and 6 evaluable patients will be required for Cohort 2 to confirm the tolerability. The total number of evaluable subjects in each cohort will depend upon available data in each cohort and decision of Safety Review Committee(SRC). Study Period: The study is expected to start in June 2019 and end in June 2020. Number of Subjects: 9 to 12 evaluable subjects will be enrolled in this study to confirm the tolerability. Treatments and treatment duration: Subjects will receive AZD4635 once daily (QD). A single dose of AZD4635 will be taken on Cycle 0 Day1 and the subsequent dose of AZD4635 will be taken from Cycle 1 Day 1 until discontinuation criterion is met. A cycle of study treatment will be defined as 21 days of continuous dosing.

Official Title
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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.

Conditions
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Advanced Solid Malignancies

Intervention / Treatment
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* Drug: AZD4635


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Adult subjects; age ≥ 20 years Histologically or cytological confirmation of a solid, malignant tumor, excluding central nervous system (CNS) tumors and lymphoma, that is refractory to standard therapy or for which no standard of care regimen currently exists Patients must have either at least one lesion that can be evaluable using RECIST v1.1 or patients with mCRPC must have measurable prostate specific antigen above normal limits (per local ranges) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Normotensive or well controlled blood pressure, with or without current antihypertensive treatment Females of child-bearing potential must use 2 highly effective methods of contraception Male patients should be willing to use barrier contraception Major Exclusion Criteria: Any investigational medicinal product or other systemic anticancer treatment within at least 4 weeks prior to the first dose of study treatment, or within 8 weeks after immunotherapy or other long half-life antibody therapy, whichever is the most appropriate and as judged by the Investigator. Evidence of recent or significant cardiovascular disease Unresolved toxicities from prior therapy greater than CTCAE Grade 1 at starting study treatment History of seizures, CNS tumors or CNS metastasis Active or prior documented autoimmune or inflammatory disorders within the past 3 years to the start of treatment Patients with prior ≥ Grade3 immune-mediated reactions Evidence of severe or uncontrolled systemic diseases Inadequate bone marrow reserve or organ function Refractory nausea and vomiting, chronic gastrointestinal diseases, or previous significant bowel resection that would preclude adequate absorption of AZD4635 History of hypersensitivity to AZD4635 or drugs with a similar chemical structure or class to AZD4635 Judgment by the Investigator that the patient should not participate in the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD4635 monotherapy<br>Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies | Drug: AZD4635<br>* AZD4635 taken orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of Adverse event and SAE | Investigate the safety and tolerability of AZD4635 | From the informed consent to 30 days post last dose | 
| The incidence of Dose-limiting toxicity (DLTs) | Investigate the safety and tolerability of AZD4635 | 25 days (Cycle0 and Cycle1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Summarize based on RECIST 1.1 by cohort and overall. | Tumor assessment is 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. | 
| Maximum plasma concentration (Cmax) | Characterize the single-dose and multiple-dose plasma of AZD4635 | Samples will be 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. | 
| Disease control rate (DCR) | Summarize based on RECIST 1.1 by cohort and overall. | Tumor assessment is 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. | 
| Area under the plasma concentration-time curve (AUC) | Characterize the single-dose and multiple-dose plasma of AZD4635 | Samples will be 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. |