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

NCT07065435 | Recruiting Phase 2

• 1 other identifier: NJMU-BC07
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Disitamab Vedotin (RC48); Bevacizumab; Pyrotinib; Trastuzumab deruxtecan failure

Outcome Measures

Primary Outcomes (1)

• 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).

  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

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  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

• Overall Survival (OS)

  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

• Duration of Response (DoR)

  From first documented response until disease progression or death, assessed up to 24 months

• Disease Control Rate (DCR)

  Assessed at 6 weeks and every 8 weeks thereafter up to 24 months

• Incidence of Treatment-Related Adverse Events

  From first dose until 30 days after last dose, assessed up to 36 months

Study Arms (2)

RC48 + Bevacizumab

EXPERIMENTAL

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.

Drug: Disitamab Vedotin (RC48); Drug: Bevacizumab

RC48 + Pyrotinib

EXPERIMENTAL

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.

Drug: Disitamab Vedotin (RC48); Drug: Pyrotinib

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.

RC48 + Bevacizumab; RC48 + Pyrotinib

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.

RC48 + Bevacizumab

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.

RC48 + Pyrotinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.

You may not qualify if:

• 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.
• Pregnant or breastfeeding women.
• 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.
• Participation in another interventional clinical trial with investigational agents not yet completed.
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• 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

Study Sites (1)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

disitamab vedotin; RC48 antibody; Bevacizumab; pyrotinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Wei Li, Ph.D

CONTACT

025-68307102; liwei1218@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: July 15, 2025
• Study Start: January 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: January 1, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

CN (1)