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

NCT ID: NCT03980821

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-04
• Study Completion Date: 2020-09-07

Brief Summary

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

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.

Conditions

Advanced Solid Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

AZD4635 monotherapy

Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies

Group Type: EXPERIMENTAL

AZD4635

Intervention Type: DRUG

AZD4635 taken orally

Interventions

AZD4635

AZD4635 taken orally

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Chūōku, , Japan

Research Site

Kashiwa, , Japan

Countries

Japan

References

Matsubara N, Kusuhara S, Yamamoto N, Sudo K, Yanagita M, Murayama K, Kawasumi H, Russell DL, Yin D, Shimizu T. Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study. Cancer Chemother Pharmacol. 2024 Apr;93(4):341-352. doi: 10.1007/s00280-023-04605-9. Epub 2023 Dec 13.

Reference Type: DERIVED

PMID: 38086998 (View on PubMed)

Other Identifiers

D8730C00005

Identifier Type: -

Identifier Source: org_study_id