Home › Trials › NCT05593094

Testing ZN-A-1041 capsules in patients with advanced HER2-positive solid tumors

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

Phase 1 Interventional Suzhou Zanrong Pharma Limited · NCT05593094

This study is testing a new drug called ZN-A-1041 to see if it can help people with advanced HER2-positive solid tumors, including those with brain metastases, either on its own or when combined with other treatments.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment210 (estimated)
Ages18 Years and up
SexAll
SponsorSuzhou Zanrong Pharma Limited Industry-sponsored
Drugs / interventionsTrastuzumab, Pertuzumab, tucatinib, afatinib, lapatinib, neratinib, pyrotinib, chemotherapy
Locations23 sites (Tucson, Arizona and 22 other locations)
Trial IDNCT05593094 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial evaluates the safety and efficacy of ZN-A-1041, both as a standalone treatment and in combination with other therapies, for patients with HER2-positive advanced solid tumors, including those with brain metastases. The study is structured in three phases: Phase 1a focuses on dose escalation of ZN-A-1041 monotherapy, Phase 1b explores combinations with established treatments, and Phase 1c expands on the most promising combinations. Patients will be assessed for eligibility based on their cancer type and previous treatments.

Who should consider this trial

Good fit: Ideal candidates are patients with unresectable or metastatic HER2-positive advanced solid tumors who have previously received standard therapies.

Not a fit: Patients with HER2-negative tumors or those who have not received prior HER2-targeted therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced HER2-positive solid tumors.

How similar studies have performed: Other studies have shown promise with similar HER2-targeted therapies, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
* Inclusion Criteria:

  1. ECOG performance status of 0 to 1
  2. HER2 positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence In Situ Hybridization (FISH) positive, or IHC (+++).
  3. Phase 1a study will enroll patients with unresectable or metastatic HER2-positive advanced solid tumor.

     For patients who have no brain metastases, the following criteria should be met:
     1. Patients should be relapsed or refractory to existing therapy(ies) or have been intolerant of such therapies
     2. Patients with HER2-positive breast cancer should have previously received Trastuzumab, Pertuzumab, Trastuzumab emtansine(T-DM1) and a taxane.
     3. Patients with HER2-positive gastric cancer must have previously received trastuzumab.
     4. Have measurable or non-measurable disease assessable by RECIST 1.1.

     For patients with brain metastasis, the following criteria should be met:
     1. Patients with HER2-positive breast cancer must have received prior treatment with Trastuzumab, Pertuzumab and T-DM1, and a taxane or patient declined the above treatment.
     2. Patients with HER2-positive gastric cancer must have previously received Trastuzumab
     3. Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT and 2 weeks from SRS; ii) Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.

     For patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks.
  4. Phase 1b and Phase 1c study will enroll patients with unresectable locally advanced or metastatic HER2+ breast cancer.

     For Phase 1b patients who have no brain metastases, the following criteria should be met:
     1. For arm 1 and arm 2, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression.
     2. Have measurable or non-measurable disease assessable by RECIST 1.1

     For Phase 1c patients who have no brain metastases, the following criteria should be met:
     1. For arm 1 and arm 2, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received a pertuzumab plus trastuzumab or T-DXd for advanced HER2+breast cancer with no evidence of disease progression.
     2. In arms 1 and 2, patients should have at least one measurable lesion either extracranially or intracranially per RECIST v1.1.

     For patients with brain metastasis, the following criteria should be met:
     1. For arm 1 and arm 2 of phase 1b, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression. For arm 1 and arm 2 of phase 1c, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received previous treatment with a pertuzumab plus trastuzumab or T-DXd for advanced HER2+ breast cancer with no evidence of disease progression (except brain metastases).
     2. Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT, 2 weeks from SRS and 4 weeks from surgery; ii) Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.
  5. Suspected or confirmed leptomeningeal metastasis are allowed.
  6. In Phase 1b arm1 and arm2, patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks. For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO and taxane.
  7. In Phase 1c arm1 and arm2, Patients should not have received prior treatment with tucatinib, afatinib, or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO or T-Dxd based induction.
* Exclusion Criteria:

  1. Subjects who have participated in any clinical study or received any clinical study drug within 4 weeks prior to the first administration except for on-going Herceptin, Perjeta or PHESGO in arm3
  2. CNS Exclusion - Based on screening brain MRI and clinical assessment

     1. Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)
     2. Any intracranial lesion thought to require immediate local therapy
     3. Require antiepileptic treatment (except for these patients with stable seizures require continuous Levetiracetam therapy).
     4. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent)

Where this trial is running

Tucson, Arizona and 22 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Solid TumorsHER2-positive Breast CancerPhase 1HER2 postiveBrain metastasesHerceptinPerjetaPHESGO
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.