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

Conditions

• HER2 + Breast Cancer

Interventions

DRUG

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.

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• RenJi Hospital

  collaborator OTHER

• Anhui Provincial Hospital

  collaborator OTHER_GOV

• The Affiliated Hospital of Xuzhou Medical University

  collaborator OTHER

• The First Hospital of Jilin University

  collaborator OTHER

• Shanghai Minhang Central Hospital

  collaborator OTHER

• Zhejiang Cancer Hospital

  collaborator OTHER

• Huai'an First People's Hospital

  collaborator OTHER

• The First Affiliated Hospital with Nanjing Medical University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-01-01

Primary Completion

2025-12-01

Completion

2026-01-01

Countries

• China

Study Locations