This multicenter, Phase II study (RADIANT-BC01) evaluates the efficacy and safety of Disitamab Vedotin (RC48) in combination with either bevacizumab or pyrotinib in adult patients with HER2-positive metastatic breast cancer whose disease has progressed on prior trastuzumab deruxtecan (T-Dxd) therapy.
Eligible participants will be randomized 1:1 to receive RC48 plus bevacizumab (7.5 mg/kg IV every 2 weeks) or RC48 plus pyrotinib (320 mg orally once daily). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or initiation of new anticancer therapy.
The primary endpoint is objective response rate (ORR); key secondary endpoints include progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety.
This study aims to identify new post-T-Dxd treatment options and improve outcomes for patients with advanced HER2-positive breast cancer.
Age ≥18 years.
Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+ with ISH amplification) advanced or metastatic breast cancer.
Prior treatment with trastuzumab deruxtecan (T-DXd) and documented disease progression during or after therapy.
At least one measurable lesion at baseline as defined by RECIST v1.1.
Prior treatment with disitamab vedotin (RC48).
Active infections requiring systemic therapy (bacterial, viral, or fungal).
History of interstitial lung disease or non-infectious pneumonitis requiring corticosteroid therapy.
Uncontrolled cardiovascular disease, including but not limited to: uncontrolled hypertension, recent myocardial infarction (within 6 months), unstable angina, or congestive heart failure.
Parallel
Disitamab Vedotin (RC48)
DrugA HER2-targeted antibody-drug conjugate comprising a humanized anti-HER2 monoclonal antibody linked via a cathepsin-cleavable MC-VC-PAB linker to the microtubule inhibitor MMAE (drug-to-antibody ratio ≈4). Administered intravenously at 2.0 mg/kg every 2 weeks.
Bevacizumab
DrugA recombinant humanized monoclonal antibody that binds vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis. Administered intravenously at 7.5 mg/kg every 2 weeks in combination with RC48.
Pyrotinib
DrugAn irreversible pan-HER tyrosine kinase inhibitor targeting HER1, HER2, and HER4, inhibiting downstream PI3K/Akt and MAPK signaling. Administered orally at 320 mg once daily (post-meal) in combination with RC48.
Objective Response Rate (ORR)
The Objective Response Rate (ORR) is defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria, as assessed by independent radiological review. Tumor assessments will be performed every 6 weeks. This endpoint evaluates the antitumor activity of RC48 in combination with either bevacizumab or pyrotinib in patients with HER2-positive advanced breast cancer who have failed prior treatment with trastuzumab deruxtecan (T-Dxd).
Progression-Free Survival (PFS)
Progression-Free Survival is defined as the time from the date of randomization to the date of first documented disease progression (per RECIST v1.1 by independent review) or death from any cause, whichever occurs first. PFS will be used to evaluate the efficacy of the combination regimens in delaying disease progression in patients with HER2-positive advanced breast cancer previously treated with trastuzumab deruxtecan.
Overall Survival (OS)
Overall Survival is defined as the time from randomization to death from any cause. Patients who are still alive at the time of analysis will be censored at the date of last follow-up. OS will provide a measure of the survival benefit of RC48 combined with either bevacizumab or pyrotinib.
Duration of Response (DoR)
Duration of Response is defined as the time from the first documentation of objective tumor response (CR or PR per RECIST v1.1) to the time of disease progression or death. Only patients with confirmed objective response will be included in this analysis.
Disease Control Rate (DCR)
Disease Control Rate is defined as the proportion of patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) lasting at least 6 weeks, based on RECIST v1.1 as assessed by independent review.
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The First Affiliated Hospital with Nanjing Medical University
Lead sponsor
RenJi Hospital
Collaborator
Anhui Provincial Hospital
Collaborator
The Affiliated Hospital of Xuzhou Medical University
Collaborator
The First Hospital of Jilin University
Collaborator
Shanghai Minhang Central Hospital
Collaborator
Zhejiang Cancer Hospital
Collaborator
Huai'an First People's Hospital
Collaborator
