Clinical trial NCT06968585: 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
Official title: A Phase III,Multicenter,Randomized,Open-Label,Active-Controlled Trial of A166 Versus Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Unresectable or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HER2-positive Breast Cancer
Lead sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-13
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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. 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Randomization up to approximately 39 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Randomization up to approximately 48 months
measure: Objective response rate(ORR)
timeFrame: Randomization up to approximately 39 months
measure: Disease control rate(DCR)
timeFrame: Randomization up to approximately 39 months
measure: Duration of response(DOR)
timeFrame: Randomization up to approximately 39 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: