A Study of A166 Versus Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Unresectable or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane Therapy

Phase 3

Active, not recruiting

• Conditions: HER2-positive Breast Cancer
• Interventions: Drug: A166; Drug: T-DM1

• Registration Number: NCT06968585
• Lead Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Brief Summary

Evaluation of the efficacy of A166 versus trastuzumab emtansine (T-DM1) in Patients with HER2-Positive unresectable or metastatic breast cancer previously treated with trastuzumab and taxane therapy

Detailed Description

This study will evaluate the efficacy of A166 versus trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and taxane therapy

To further evaluate the efficacy of A166 versus T-DM1 in patients with HER2-positive unresectable or metastatic breast cancer, based on effectiveness endpoints including:

Overall survival (OS)

Progression-free survival (PFS) as assessed by investigators

Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and clinical benefit rate (CBR) assessed by both blinded independent central review (BICR) and investigators.

To assess the safety profile of A166 for injection in patients with HER2-positive unresectable or metastatic breast cancer.

To evaluate the immunogenicity of A166 for injection in patients with HER2-positive unresectable or metastatic breast cancer.

To characterize the pharmacokinetic (PK) profile of A166 for injection in patients with HER2-positive unresectable or metastatic breast cancer.

Study Timeline

• Study Start: 2023-07-18
• Status Verified: 2025-04
• Study First Submitted: 2025-04-26
• Study First Submitted QC: 2025-05-05
• Last Update Submitted: 2025-05-05
• Study First Posted: 2025-05-13
• Last Update Posted: 2025-05-13
• Primary Completion: 2025-11-30
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 365

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. Disease progression after receiving a trastuzumab-based regimen (or a commercially available trastuzumab biosimilar or inetetamab) in the advanced or metastatic setting, or disease progression/recurrence within 12 months during or after (neo)adjuvant therapy (with a trastuzumab-based regimen or commercially available trastuzumab biosimilar).
4. Have previously received taxanes.
5. Patients must have experienced disease progression or intolerance during or after the most recent treatment prior to randomization.
6. 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 , T-DM1 (trastuzumab emtansine) 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A166	A166	A166 is administered intravenously at a dose of 4.8 mg/kg every 21 (±3) days (q3w).
T-DM1	T-DM1	T-DM1 is administered intravenously at a dose of 3.6 mg/kg every 21 (±3) days (q3w).

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Randomization up to approximately 39 months	PFS as assessed by BICR according to RECIST v 1.1

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Randomization up to approximately 48 months	OS, 1-year survival rate, 2-year survival rate, and 3-year survival rate.
Objective response rate(ORR)	Randomization up to approximately 39 months	ORR is defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by BICR/investigator per RECIST 1.1
Disease control rate(DCR)	Randomization up to approximately 39 months	DCR is defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by BICR/investigator per RECIST 1.1
Duration of response(DOR)	Randomization up to approximately 39 months	DoR is defined as the time from the date of first documented CR or PR until date of documented disease progression per RECIST 1.1, as assessed by BICR/investigator or death due to any cause, whichever occurs first.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China