NCT07366840

RC48 Combined With Chemotherapy in HER2-Positive Advanced Breast Cancer Patients With Prior TOP1i-ADC Failure

A Phase 3, Randomized Advanced Breast Cancer Study Investigating RC48 Combined With Chemotherapy Versus Guideline-recommended Trastuzumab/Inetetamab Plus Chemotherapy in HER2-Positive Patients With Prior TOP1i-ADC Failure

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 268 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the safety and efficacy of RC48 (a HER2 antibody drug conjugate with MMAE payload) in combination with gemcitabine or capecitabine (with or without trastuzumab/inetetamab), for treatment of patients with HER2-positive advanced breast cancer (ABC) who have developed disease progression or intolerance to prior therapy with a topoisomerase I inhibitor antibody-drug conjugate (TOP1i-ADC).

Detailed description

This is a randomized, open-label, parallel-controlled, multi-centered, phase 3 clinical study enrolling patients with HER2-positive ABC who have experienced disease progression or intolerance to prior TOP1i-ADC treatment, with ≤ 3 lines of systemic therapy received in the recurrent/metastatic setting. The study consists of two main parts: Part 1: Run-in Phase and Part 2: Randomized Controlled Trial. Part 1: Run-in Phase The primary objective of the Run-in Phase is to preliminarily verify whether the addition of trastuzumab or inetetamab to the combination regimen of RC48 plus chemotherapy can enhance the anti-tumor efficacy and whether it is associated with any specific toxicities. This phase comprises two regimens, and 30 patients will be randomized 1:1 to receive treatment with either of the two regimens: RC48 plus Gemcitabine or Capecitabine; RC48 plus Gemcitabine or Capecitabine, plus Trastuzumab or Inetetamab. . Part 2: Randomized Controlled Trial The primary objective of this part is to assess the anti-tumor activity and safety of the optimal regimen identified in Part 1 in patients with HER2-positive ABC who have failed prior TOP1i-ADC treatment. Eligible patients will be stratified and randomized 1:1 to either the experimental group or the control group. 238 patients are expected to be enrolled in Part 2. Experimental group: RC48 plus Gemcitabine or Capecitabine ± Trastuzumab or Inetetamab. Control group: Trastuzumab or Inetetamab plus Gemcitabine or Capecitabine.

Conditions

• HER2-positive Breast Cancer
• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Disitamab Vedotin	2.0mg/kg every two weeks
DRUG	Gemcitabine	1000mg/m2 on days 1 and 8 every three weeks
DRUG	Capecitabine	1000 mg/m2 twice daily on days 1 to14 every three weeks
DRUG	Trastuzumab	6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg
DRUG	Inetetamab	6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg

Timeline

• Start date: 2026-01-16
• Primary completion: 2028-01-16
• Completion: 2029-01-16
• First posted: 2026-01-26
• Last updated: 2026-01-26