Suspended

ZN-A-1041 Enteric Capsules for HER2-Positive Advanced Solid Tumors

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Study AimThis study evaluates the safety and effectiveness of ZN-A-1041 capsules, alone or in combination with other treatments, in people with advanced HER2-positive solid tumors to find the best dose with the fewest side effects.
What is being tested

ZN-A-1041

+ ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b
+ ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b
Drug
Who is being recruted

Brain Diseases
+5

+ Brain Neoplasms
+ Central Nervous System Diseases
Over 18 Years
+7 Eligibility Criteria
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: September 2020
See protocol details

Summary

Principal SponsorHoffmann-La Roche
Last updated: December 13, 2025
Sourced from a government-validated database.Claim as a partner
Study start date: September 3, 2020Actual date on which the first participant was enrolled.

This clinical trial focuses on evaluating a new treatment option, ZN-A-1041, for individuals with advanced solid tumors that have a specific feature known as HER2-positive. HER2-positive tumors are known to be aggressive and challenging to treat, so finding effective therapies is crucial. This study is important because it aims to determine the safest and most effective way to use ZN-A-1041, both on its own and in combination with other established cancer treatments. This could potentially lead to better treatment outcomes and improve quality of life for patients with these types of cancers. During the study, participants will receive ZN-A-1041 in capsule form. The trial is divided into three phases. Initially, the drug will be administered alone in gradually increasing doses to determine the maximum safe dose. Next, ZN-A-1041 will be combined with standard treatments like T-DM1, T-DXd, or combinations of other cancer drugs to find the best dosing strategy. Finally, more participants will join to further assess how well these combinations work. Throughout the study, researchers will monitor participants for any side effects and measure the drug's impact on the tumors, ensuring any adverse effects are manageable and evaluating the overall safety and effectiveness of the treatment.

Official TitleA 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 
NCT05593094
Principal SponsorHoffmann-La Roche
Last updated: December 13, 2025
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
210 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are assigned to groups based on specific criteria, such as their medical history or a doctor's recommendation. This approach ensures that treatments are given to those who may benefit the most, based on known factors.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants receive treatments one after another in a pre-planned sequence. The next treatment may depend on how the participant responds to the previous one.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Brain Diseases
Brain Neoplasms
Central Nervous System Diseases
Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Central Nervous System Neoplasms
Criteria
5 inclusion criteria required to participate
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

Show More Criteria

2 exclusion criteria prevent from participating
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

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
7 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
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).

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

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)
Group III
Experimental
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.

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)
Group IV
Experimental
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.

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
Group 5
Experimental
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.

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)
Group 6
Experimental
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.

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)
Group 7
Experimental
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.

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

Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.

Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.

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.
Secondary Objectives

To assess the PK of ZN-A-1041 and its major metabolites.

To assess the serum concentration of combination drugs.

To assess the incidence of ADAs.

The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.

The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 36 locations
Suspended
Arizona Clinical Research Center, Inc.;Hematology Oncology Physicians - AoaTucson, United StatesSee the location
Suspended
TOI Clinical ResearchCerritos, United States
Suspended
UCSF Helen Diller Family CCCSan Francisco, United States
Suspended
Dana Farber Cancer InstituteBoston, United States
Suspended36 Study Centers
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