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

NCT ID: NCT05593094

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-03

Study Completion Date

2026-07-31

Brief Summary

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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

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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

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Advanced Solid Tumors HER2-positive Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1a: ZN-A-1041

Phase 1a:

Participants will receive escalating doses of ZN-A-1041 orally twice a day (BID) at pre-defined dosing regimens to determine the maximum tolerated dose (MTD).

Group Type EXPERIMENTAL

ZN-A-1041

Intervention Type DRUG

ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD

1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.

Phase 1b Arm1:

1. If the maximum tolerated dose (MTD) of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).
2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Group Type EXPERIMENTAL

ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b

Intervention Type DRUG

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)

1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.

Phase 1b Arm2:

1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).
2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Group Type EXPERIMENTAL

ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b

Intervention Type DRUG

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)

1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta

Phase 1b Arm3:

1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2).
2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Group Type EXPERIMENTAL

ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1b

Intervention Type DRUG

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

1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.

Phase 1c Arm1:

The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.

Group Type EXPERIMENTAL

ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1c

Intervention Type DRUG

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)

1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.

Phase 1c Arm2:

The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.

Group Type EXPERIMENTAL

ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1c

Intervention Type DRUG

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)

1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO

Phase 1c Arm3:

The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.

Group Type EXPERIMENTAL

ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1c

Intervention Type DRUG

ZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion

Interventions

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ZN-A-1041

ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD

Intervention Type 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)

Intervention Type 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)

Intervention Type 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

Intervention Type 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)

Intervention Type 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)

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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ZN-A-1041 Enteric Capsules ZN-A-1041 Enteric Capsules ZN-A-1041 Enteric Capsules ZN-A-1041 Enteric Capsules ZN-A-1041 Enteric Capsules ZN-A-1041 Enteric Capsules ZN-A-1041 Enteric Capsules

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of at least 6 months, as determined by the investigator
* Histologically or cytologically confirmed with unresectable or metastatic HER2-positive advanced solid tumors
* Must be relapsed or refractory after prior treatment for metastatic disease that included a taxane and trastuzumab or must have received first-line induction therapy for advanced disease a pertuzumab plus trastuzumab-based regimen or a T-DXd-based regimen
* Participants with new, untreated, progressive, or stable brain metastases are eligible

Exclusion Criteria

* Participation in any other clinical study involving an investigational drug or device within 4 weeks prior to the first dose of study treatment
* Any intracranial lesion (brain metastasis) that requires immediate local therapy, such as surgery or radiation, or systemic corticosteroids at the time of enrollment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Arizona Clinical Research Center, Inc.;Hematology Oncology Physicians - Aoa

Tucson, Arizona, United States

Site Status

TOI Clinical Research

Cerritos, California, United States

Site Status

UCSF Helen Diller Family CCC

San Francisco, California, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Hospital

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Duke University School of Medicine

Durham, North Carolina, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Geelong Hospital

Geelong, Victoria, Australia

Site Status

Sunshine Hospital

St Albans, Victoria, Australia

Site Status

EDOG - Institut Claudius Regaud - PPDS

Toulouse, Haute-Garonne, France

Site Status

Centre Georges Francois Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes

Lyon, , France

Site Status

Institut Paoli-Calmettes

Marseille, , France

Site Status

Institut de Cancerologie de l Ouest

Saint-Herblain, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS

Parma, Emilia-Romagna, Italy

Site Status

Asst Papa Giovanni XXIII

Bergamo, Lombardy, Italy

Site Status

Fondazione Policlinico Universitario A Gemelli-Rome

Magnago, Lombardy, Italy

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Argentona, Barcelona, Spain

Site Status

Hospital Clinico Universitario de Santiago

Santiago de Compostela, LA Coruna, Spain

Site Status

Hospital Universitario Ramon y Cajal

A Gudiña, Orense, Spain

Site Status

Hospital Universitario Virgen del Rocio

Las Cabezas de San Juan, Sevilla, Spain

Site Status

Instituto Oncologico Dr. Rosell-Hospital Universitari Dexeus-Grupo Quironsalud

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario de Jaen

Jaén, , Spain

Site Status

Hospital Beata Maria Ana

Madrid, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Fundacion Instituto Valenciano de Oncologia (IVO)

Valencia, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

The Christie

Manchester, Lancashire, United Kingdom

Site Status

Clatterbridge Cancer Centre

Liverpool, Merseyside, United Kingdom

Site Status

Countries

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United States Australia France Italy New Zealand Spain United Kingdom

Other Identifiers

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ZN-A-1041-101-US

Identifier Type: OTHER

Identifier Source: secondary_id

2023-508459-37-00

Identifier Type: CTIS

Identifier Source: secondary_id

XO45189

Identifier Type: -

Identifier Source: org_study_id

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