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

May 22, 2026 updated by: Hoffmann-La Roche

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

210

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Geelong, Victoria, Australia, 3220
        • Geelong Hospital
      • St Albans, Victoria, Australia, 3021
        • Sunshine Hospital
  • France
      • Dijon, France, 21000
        • Centre Georges Francois Leclerc
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
      • Marseille, France, 13009
        • Institut Paoli-Calmettes
      • Saint-Herblain, France, 44805
        • Institut de Cancerologie de l Ouest
      • Villejuif, France, 94800
        • Gustave Roussy
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31059
        • EDOG - Institut Claudius Regaud - PPDS
  • Italy
    • Emilia-Romagna
      • Parma, Emilia-Romagna, Italy, 43126
        • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS
    • Lombardy
      • Bergamo, Lombardy, Italy, 24127
        • Asst Papa Giovanni XXIII
      • Magnago, Lombardy, Italy, 20020
        • Fondazione Policlinico Universitario A Gemelli-Rome
  • New Zealand
      • Auckland, New Zealand, 1023
        • Auckland City Hospital
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spain, 08028
        • Instituto Oncologico Dr. Rosell-Hospital Universitari Dexeus-Grupo Quironsalud
      • Jaén, Spain, 23007
        • Hospital Universitario de Jaén
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital Beata Maria Ana
      • Seville, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46009
        • Fundacion Instituto Valenciano de Oncologia (IVO)
    • Barcelona
      • Argentona, Barcelona, Spain, 08310
        • Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
    • LA Coruna
      • Santiago de Compostela, LA Coruna, Spain, 15706
        • Hospital Clínico Universitario de Santiago
    • Orense
      • A Gudiña, Orense, Spain, 32540
        • Hospital Universitario Ramon y Cajal
    • Sevilla
      • Las Cabezas de San Juan, Sevilla, Spain, 41730
        • Hospital Universitario Virgen del Rocio
  • United Kingdom
    • Lancashire
      • Manchester, Lancashire, United Kingdom, M20 4BX
        • The Christie
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L69 3GL
        • Clatterbridge Cancer Centre
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85712
        • Arizona Clinical Research Center, Inc.;Hematology Oncology Physicians - Aoa
    • California
      • Cerritos, California, United States, 90703-2684
        • TOI Clinical Research
      • San Francisco, California, United States, 94158
        • UCSF Helen Diller Family CCC
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Hospital
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University School of Medicine
    • Texas
      • Houston, Texas, United States, 77030-4000
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: ZN-A-1041
ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD
Other Names:
  • ZN-A-1041 Enteric Capsules
Experimental: 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.
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)
Other Names:
  • ZN-A-1041 Enteric Capsules
Experimental: 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.
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)
Other Names:
  • ZN-A-1041 Enteric Capsules
Experimental: 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.
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
Other Names:
  • ZN-A-1041 Enteric Capsules
Experimental: 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.
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)
Other Names:
  • ZN-A-1041 Enteric Capsules
Experimental: 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.
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)
Other Names:
  • ZN-A-1041 Enteric Capsules
Experimental: 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.
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
Other Names:
  • ZN-A-1041 Enteric Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a
Time Frame: 23 days
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
23 days
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 in Combination with T-DM1 or with T-DXd, or in Combination with PHESGO or Herceptin plus Perjeta
Time Frame: 21 days
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
21 days
RP2D
Time Frame: Through study completion, an average of 1 year
To evaluate the safety of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta in participants on the RP2D.
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma, Urine and Potentially Cerebrospinal Fluid (CSF) Level of ZN-A-1041 and its Main Metabolites
Time Frame: From baseline to cycle 9 (each cycel is 21 days)
To assess the PK of ZN-A-1041 and its major metabolites.
From baseline to cycle 9 (each cycel is 21 days)
Serum Level of Combination Drugs in Phase 1c
Time Frame: Through study completion, an average of 2 year
To assess the serum concentration of combination drugs.
Through study completion, an average of 2 year
Anti-drug Antibodies (ADAs) Evaluation in Phase 1c
Time Frame: Through study completion, an average of 2 year
To assess the incidence of ADAs.
Through study completion, an average of 2 year
Overall Response Rate (ORR)
Time Frame: Through study completion, an average of 2 year
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
Through study completion, an average of 2 year
Progression Free Survival (PFS)
Time Frame: Through study completion, an average of 2 year
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
Through study completion, an average of 2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2020

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

August 31, 2027

Study Registration Dates

First Submitted

October 17, 2022

First Submitted That Met QC Criteria

October 22, 2022

First Posted (Actual)

October 25, 2022

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XO45189
  • ZN-A-1041-101-US (Other Identifier: Suzhou Zanrong Pharma Limited)
  • 2023-508459-37-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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