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NCT Number: 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

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).

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Key information

Conditions

Advanced Solid Tumors Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms HER2-positive Breast Cancer Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Geelong Hospital, Geelong, Victoria, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ZN-A-1041

Drug

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

Other names: ZN-A-1041 Enteric Capsules

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

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)

Other names: ZN-A-1041 Enteric Capsules

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

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)

Other names: ZN-A-1041 Enteric Capsules

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

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

Other names: ZN-A-1041 Enteric Capsules

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

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)

Other names: ZN-A-1041 Enteric Capsules

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

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)

Other names: ZN-A-1041 Enteric Capsules

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

Drug

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

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. Anti-drug Antibodies (ADAs) Evaluation in Phase 1c

    Time frame: Through study completion, an average of 2 year

    To assess the incidence of ADAs.

  4. 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.

  5. 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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
Oct 25, 2022
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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