NCT05593094

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors

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

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 210 (estimated)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 participants 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).

Detailed description

This study is composed of three parts designed to evaluate the safety and efficacy of ZN-A-1041 in participants with HER2-positive advanced solid tumors. Phase 1a (Monotherapy Dose Escalation): In this first phase, participants will receive ZN-A-1041 alone. The study will begin with a low dose of ZN-A-1041, which will be gradually increased in new groups of participants to find the highest dose that can be given safely. This will establish the recommended dose for further study. Phase 1b (Combination Dose Escalation): In the second phase, the study will evaluate the safety of giving ZN-A-1041 together with established standard-of-care therapies for HER2-positive breast cancer. Participants will be enrolled into one of three combination arms to receive ZN-A-1041 with either T-DM1, T-DXd, or a pertuzumab/trastuzumab-based regimen. This phase will identify the recommended dose for these combination therapies. Phase 1c (Combination Dose Expansion): In the final phase, additional participants will be enrolled to receive ZN-A-1041 at the recommended combination doses identified in Phase 1b. This will allow for a more thorough evaluation of the safety and preliminary efficacy of these treatment regimens. Throughout the study, participants will undergo screening, treatment, and follow-up periods to collect comprehensive data on the safety, tolerability, pharmacokinetics, and anti-tumor activity of ZN-A-1041, both as a single agent and in combination.

Conditions

• Advanced Solid Tumors
• HER2-positive Breast Cancer

Interventions

Type	Name	Description
DRUG	ZN-A-1041	ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD
DRUG	ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b	ZN-A-1041: BID via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
DRUG	ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b	ZN-A-1041: BID via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
DRUG	ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1b	ZN-A-1041: BID via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion
DRUG	ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1c	ZN-A-1041: BID via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
DRUG	ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1c	ZN-A-1041: BID via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
DRUG	ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1c	ZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion

Timeline

• Start date: 2020-09-03
• Primary completion: 2027-07-31
• Completion: 2027-07-31
• First posted: 2022-10-25
• Last updated: 2026-02-25

Locations

36 sites across 7 countries: United States, Australia, France, Italy, New Zealand, Spain, United Kingdom

Regulatory

• FDA-regulated drug study