What side effects are associated with this type of intervention?

Common treatments for HER2-positive breast cancer, such as trastuzumab, pertuzumab, trastuzumab-emtansine (T-DM1), and fam-trastuzumab deruxtecan, are associated with several side effects. Trastuzumab and pertuzumab can cause cardiac dysfunction, including reduced left ventricular ejection fraction. T-DM1 may lead to thrombocytopenia, elevated liver enzymes, and fatigue. Fam-trastuzumab deruxtecan has been linked to interstitial lung disease, nausea, and decreased neutrophil count. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for HER2-positive breast cancer. Trastuzumab (Herceptin) was one of the first, showing significant improvement in progression-free survival (PFS) and overall survival (OS) when combined with chemotherapy. Pertuzumab (Perjeta) is another HER2-targeted therapy often used in combination with trastuzumab and chemotherapy, further improving outcomes. Ado-trastuzumab emtansine (Kadcyla) and fam-trastuzumab deruxtecan (Enhertu) are antibody-drug conjugates approved for patients who have progressed on prior HER2-targeted treatments. Neratinib, in combination with capecitabine, is also approved for advanced HER2-positive breast cancer after two or more prior anti-HER2 regimens.

What other types of research exist?

Promising novel alternatives to ZN-A-1041 for HER2-positive breast cancer patients include: 1) Trastuzumab deruxtecan (T-DXd), which has shown CNS activity and is often sequenced before T-DM1. 2) Tucatinib in combination with capecitabine and trastuzumab, which has improved progression-free survival and overall survival in patients with brain metastases. 3) Neratinib and capecitabine or lapatinib plus capecitabine, which are supported by phase II studies as effective alternatives.

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ZN-A-1041 Combinations for Breast Cancer

Phase 1

Recruiting

Led By Anders Carey K, MD

Research Sponsored by Suzhou Zanrong Pharma Limited

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

HER2 positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence In Situ Hybridization (FISH) positive, or IHC (+++).

- Patients with HER2-positive gastric cancer must have previously received trastuzumab.

Must not have

- Any intracranial lesion thought to require immediate local therapy

- Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 2 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called ZN-A-1041 to see if it is safe and effective for patients with advanced cancers that have a specific marker called HER2. The drug aims to find and destroy these cancer cells, even if they have spread to the brain.

Who is the study for?

This trial is for adults with advanced HER2-positive solid tumors, including breast and gastric cancers. Participants must have tried certain treatments like Trastuzumab or a taxane without success, or be intolerant to them. Those with brain metastases can join if they meet specific criteria regarding prior treatments and stability of their condition.

What is being tested?

The trial tests ZN-A-1041 alone or in combination with other cancer drugs (T-DM1, PHESGO/Herceptin plus Perjeta, T-Dxd) at various doses to assess safety, tolerability, how the body processes the drug (pharmacokinetics), and effectiveness against HER2-positive tumors.

What are the potential side effects?

Potential side effects are not listed but may include typical reactions to cancer therapies such as nausea, fatigue, allergic reactions to medication components, infusion-related symptoms from IV drugs, and possible interactions when combined with other treatments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is HER2 positive based on specific tests.

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I have HER2-positive stomach cancer and was treated with trastuzumab.

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I am fully active or can carry out light work.

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I have an advanced solid tumor that is HER2-positive and cannot be surgically removed.

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I have had Trastuzumab, Pertuzumab, T-DM1, and a taxane for my HER2-positive breast cancer.

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I have HER2-positive breast cancer and have been treated with or declined Trastuzumab, Pertuzumab, T-DM1, and a taxane.

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I have HER2-positive stomach cancer and was treated with Trastuzumab.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a brain lesion that needs immediate treatment.

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I am experiencing worsening neurological symptoms like headaches or blurred vision.

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I am taking more than 2 mg of dexamethasone daily for brain metastases.

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My brain MRI and clinical assessment show I don't have CNS issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 2 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 2 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 2 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

RP2D Dose

The Incidence of Treatment-Emergent Adverse Events of ZN-A-1041 as a monotherapy in Phase 1a

Gilles de la Tourette syndrome

Secondary study objectives

Anti-drug antibodies (ADAs) evaluation in Phase 1c

Plasma, urine and potentially CSF level of ZN-A-1041 and its main metabolites

Progression free survival(PFS)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

13Treatment groups

Experimental Treatment

Group I: ZN-A-1041 800mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 800mg Bid, for 21days as one cycle

Group II: ZN-A-1041 600mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 600mg Bid, for 21days as one cycle

Group III: ZN-A-1041 50mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 50mg Bid, for 21days as one cycle

Group IV: ZN-A-1041 400mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 400mg Bid, for 21days as one cycle

Group V: ZN-A-1041 200mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 200mg Bid, for 21days as one cycle

Group VI: ZN-A-1041 100mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 100mg Bid, for 21days as one cycle

Group VII: ZN-A-1041 1000mgExperimental Treatment1 Intervention

Phase 1a: Subjects will be given ZN-A-1041 orally 1000mg Bid, for 21days as one cycle

Group VIII: 1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.Experimental Treatment1 Intervention

Phase 1c Arm2: The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.

Group IX: 1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.Experimental Treatment1 Intervention

Phase 1c Arm1: The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.

Group X: 1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGOExperimental Treatment1 Intervention

Phase 1c Arm3: The dose levels of ZN-A-1041 in the Phase 1c study will be the recommended doses determined in the Phase 1b study.

Group XI: 1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.Experimental Treatment1 Intervention

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 XII: 1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.Experimental Treatment1 Intervention

Phase 1b Arm1: 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 XIII: 1b: ZN-A-1041 + PHESGO / Herceptin plus PerjetaExperimental Treatment1 Intervention

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.

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for HER2-positive breast cancer include targeted therapies such as Trastuzumab, Lapatinib, and Pertuzumab. These drugs work by binding to the HER2 receptor on cancer cells, inhibiting their growth and survival. Trastuzumab, for example, blocks the HER2 receptor, preventing cell proliferation and inducing immune-mediated cell death. Lapatinib inhibits both HER2 and EGFR pathways, disrupting cancer cell signaling. Understanding these mechanisms is crucial for patients as it helps in selecting the most effective treatment, managing potential side effects like cardiomyopathy, and overcoming drug resistance, thereby improving overall outcomes.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Sequencing for an interdisciplinary molecular tumor board in patients with advanced breast cancer: experiences from a case series.Dasatinib : a novel therapy for breast cancer?