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

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.