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

NCT03980821 | Completed Phase 1

• 1 other identifier: D8730C00005
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Solid Malignancies

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Objective response rate (ORR)

  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)

  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)

  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)

  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.

Study Arms (1)

AZD4635 monotherapy

EXPERIMENTAL

Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies

Drug: AZD4635

Interventions

AZD4635 DRUG

AZD4635 taken orally

AZD4635 monotherapy

Eligibility Criteria

• Age: 20 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Kashiwa, 277-8577, Japan

Location

Related Publications (1)

• 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.

  PMID: 38086998 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: June 10, 2019
• Study Start: July 4, 2019
• Primary Completion: September 7, 2020
• Study Completion: September 7, 2020
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

JP (2)