A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title: A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors

Status Recruiting

Clinical Trial Summary

This will be a Phase 1, multicenter, open-label trial to evaluate the safety, tolerability, PK and efficacy of ZN-A-1041 as a monotherapy or in combination in patients with HER2-positive advanced solid tumors with or without brain metastases.

The study will consist of three phases: Phase 1a (dose escalation with ZN-A-1041 monotherapy), Phase 1b (dose escalation with ZN-A-1041 combination therapy) and Phase 1c (dose expansion with ZN-A-1041 combination therapy).

Clinical Trial Description

Phase 1a of the study will adopt the "modified 3+3" dose escalation design with a total of 7 planned dose levels. Patients with HER2-positive advanced solid tumor (including those with brain metastases) will be enrolled to receive a single-dose administration of ZN-A-1041 followed by multiple-dose administration of ZN-A-1041.Phase 1b of the study will adopt the "traditional 3+3" dose escalation design. The dose levels will be based on the results of the Phase 1a study and the results of a food effect study. In Phase 1b, patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis will be enrolled in three arms: Arm1 will receive multiple doses of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with T-DXd. Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta and 4-8-cycle treatment of taxane Patients will be assigned to an appropriate arm by the sponsor and the investigator based on his/her eligibility at the time of consent. Patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis are planned to be enrolled in Phase 1c of the study: Arm1 will receive multiple doses of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with T-DXd; Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta and 4-8-cycle treatment of taxane. Patients will be assigned to an appropriate arm by the sponsor and the investigator based on his/her eligibility at the time of consent. Arm1 of Phase 1c can start independently after the DLT observation period of the last patient in Phase 1b Arm1. Arm 2 of Phase 1c can start independently after the DLT observation of the last patient in Phase 1b Arm 2. Arm 3 of Phase 1c can start independently after the DLT observation of the last patient in Phase 1b Arm 3. The dose levels used in Phase 1c will be based on the recommended doses obtained from the Phase 1b study.

Each phase of the study includes a screening period (from 28 days prior to the first administration of the study drug), a treatment period (until there are no clinical benefits as deemed by the Investigator, disease progression, death, intolerable toxicity, withdrawal of informed consent, loss of follow-up, or the start of new anti-tumor treatment), and a follow-up period (until 28 days after the last administration of the study drug). During the trial, the safety, tolerability, PK and efficacy data of ZN-A-1041 as monotherapy and in combination in the subjects will be collected and analyzed, thereby providing RP2D for subsequent future clinical trials. ;

Related Conditions & MeSH terms

• Advanced Solid Tumors
• HER2-positive Breast Cancer
• Neoplasms

• NCT number: NCT05593094
• Study type: Interventional
• Source: Suzhou Zanrong Pharma Limited
• Contact: Ding Zhou, Ph.D
• Phone: (86)-13916360900
• Email: ding.zhou@zionpharma.com
• Status: Recruiting
• Phase: Phase 1
• Start date: October 15, 2020
• Completion date: October 30, 2024