The First Affiliated Hospital with Nanjing Medical University
Phase
Phase 2
Started
2024-01-01
Last updated
2025-07-15
Condition(s) studied
HER2 + Breast Cancer
Investigational drug(s) / intervention(s)
Disitamab Vedotin (RC48)BevacizumabPyrotinib
Disitamab Vedotin (RC48): A 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: A 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: An 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.
Study summary
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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria:
1. Age ≥18 years.
2. Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+ with ISH amplification) advanced or metastatic breast cancer.
3. Prior treatment with trastuzumab deruxtecan (T-DXd) and documented disease progression during or after therapy.
4. At least one measurable lesion at baseline as defined by RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Adequate organ and marrow function, including:
Absolute neutrophil count ≥1.5 × 10⁹/L Platelet count ≥100 × 10⁹/L Hemoglobin ≥9 g/dL ALT and AST ≤2.5 × ULN Total bilirubin ≤1.5 × ULN Creatinine clearance ≥50 mL/min Estimated life expectancy of ≥12 weeks. Ability to understand and willingness to sign a written informed consent form.
Exclusion Criteria:
1. Prior treatment with disitamab vedotin (RC48).
2. Active infections requiring systemic therapy (bacterial, viral, or fungal).
3. History of interstitial lung disease or non-infectious pneumonitis requiring corticosteroid therapy.
4. Uncontrolled cardiovascular disease, including but not limited to: uncontrolled hypertension, recent myocardial infarction (within 6 months), unstable angina, or congestive heart failure.
5. Pregnant or breastfeeding women.
6. Concurrent malignancy other than adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless disease-free for ≥5 years.
7. Participation in another interventional clinical trial with investigational agents not yet completed.
8. Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements or jeopardize their safety.
Primary outcome measure(s)
Objective Response Rate (ORR) — From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months 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).
Trial sites (1)
Facility
City
Region
Status
The First Affiliated Hospital with Nanjing Medical University
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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