A166 for HER2-positive advanced or metastatic breast cancer

Phase 2 Study of A166 in HER2-positive Metastatic Breast Cancer Patients Who Were Previously Treated With TOP1-ADCs

This trial will test whether A166 helps adults with HER2-positive unresectable or metastatic breast cancer who previously received a topoisomerase inhibitor–based HER2 antibody-drug conjugate.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (industry)
• Drugs / interventions: trastuzumab
• Locations: 1 site (Zhenzhou, Henan)
• Trial ID: NCT07299825 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives intravenous A166 every three weeks to adults with HER2-positive unresectable or metastatic breast cancer who have progressed after prior therapy, including at least one HER2 ADC with a topoisomerase inhibitor payload. Eligible patients are 18–75 years old, have measurable disease by RECIST 1.1, and have received no more than five prior lines of systemic therapy. Key exclusions include prior A166 or any HER2-directed ADC with a microtubule inhibitor payload, severe hypersensitivity to monoclonal antibodies, permanent discontinuation of trastuzumab for toxicity, or significant corneal epithelial disease. The study will measure anti-tumor activity and clinical outcomes on a schedule of Q3W IV dosing at a single lead site in Henan, China.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed HER2-positive unresectable or metastatic breast cancer, at least one measurable lesion, prior treatment including a HER2 ADC with a topoisomerase inhibitor payload, and up to five prior systemic therapy lines are ideal candidates.

Not a fit: Patients previously treated with A166 or with prior HER2 ADCs carrying a microtubule inhibitor payload, those with severe baseline corneal epithelial disease, or those who had to permanently stop trastuzumab for toxicity are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, A166 could shrink tumors or delay disease progression in patients whose cancer progressed after prior HER2-targeted ADCs with topoisomerase inhibitors.

How similar studies have performed: Other HER2-targeted ADCs (for example trastuzumab deruxtecan) have shown strong activity in HER2-positive breast cancer, but the benefit of a new ADC like A166 after prior TOP1-ADC exposure is less well established.

Eligibility criteria

Inclusion Criteria:

1. Male or female patient ≥ 18 years and ≤ 75 years when signing the informed consent form.
2. Breast cancer patients by histopathology and/or cytology documented.
3. In the advanced or metastatic stage, having received no more than 5 lines of systemic therapy, one of which must include a HER2 ADC with a topoisomerase inhibitor payload.
4. Patients must have experienced disease progression or intolerance during or after the most recent treatment prior to randomization.
5. At least one measurable lesion according to RECIST 1.1 criteria.

Exclusion Criteria:

1. Previous treatment with A166 or any HER2-targeted antibody-drug conjugate (ADC) with a microtubule inhibitor payload.
2. Known history of severe hypersensitivity to other monoclonal antibodies, or allergy to A166 or their components.
3. Permanent discontinuation of trastuzumab or its biosimilars due to any toxicity in prior treatments.
4. Presence of severe corneal epithelial disease at baseline; or inability to perform daily activities without contact lenses.
5. Presence of spinal cord compression or clinically active central nervous system (CNS) metastases.
6. Other conditions considered by the investigator to make the patient unsuitable for participation in the study.

Where this trial is running

Zhenzhou, Henan

• Henan Provincial Cancer Hospital — Zhenzhou, Henan, China (RECRUITING)

Study contacts

• Study coordinator: Min Yan, Professor

Conditions: Her 2 Positive Breast Cancer