RC48 Plus Bevacizumab or Pyrotinib in HER2-Positive Metastatic Breast Cancer After T-DXd Failure: A Phase II Study

Sponsor
The First Affiliated Hospital with Nanjing Medical University
Study ID
NCT07065435
Phase
PHASE2
Status
Recruiting
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Conditions

  • HER2 + Breast Cancer

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Disitamab Vedotin (RC48) — DRUG
    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 — DRUG
    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 — DRUG
    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 Details

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.

Key Dates

First listed
Jul 15, 2025
Start date
Jan 1, 2024
Status verified
Jun 2025
Primary completion
Dec 1, 2025
Completion
Jan 1, 2026

Study Design

Enrollment
74 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: RC48 + Bevacizumab
    Participants receive Disitamab Vedotin (RC48) at 2.0 mg/kg IV every 2 weeks plus Bevacizumab 7.5 mg/kg IV every 2 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or initiation of new anticancer therapy.
  • Experimental: RC48 + Pyrotinib
    Participants receive Disitamab Vedotin (RC48) at 2.0 mg/kg IV every 2 weeks plus Pyrotinib 320 mg orally once daily (post-meal). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or initiation of new anticancer therapy.

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: 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 ]

Central Contacts

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