RC48 with bevacizumab or pyrotinib for HER2-positive metastatic breast cancer after T-Dxd failure

Efficacy and Safety of Disitamab Vedotin (RC48) in Combination With Bevacizumab or Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer After Trastuzumab Deruxtecan (T-DXd) Treatment Failure: A Phase II Study

This trial will try RC48 together with either bevacizumab or pyrotinib in adults with HER2-positive metastatic breast cancer whose disease has progressed after trastuzumab deruxtecan (T-Dxd).

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: trastuzumab, disitamab, bevacizumab, pyrotinib
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07065435 on ClinicalTrials.gov

What this trial studies

RADIANT-BC01 is a multicenter Phase II, randomized 1:1 trial testing disitamab vedotin (RC48) combined with either bevacizumab or pyrotinib in patients who progressed on T-Dxd. Participants receive RC48 plus bevacizumab intravenously every two weeks or RC48 plus daily oral pyrotinib, with treatment continued until progression, unacceptable toxicity, or withdrawal. The study uses parallel Simon two-stage cohorts for each arm to screen for sufficient objective responses, with ORR as the primary endpoint and PFS, DCR, DOR, OS, and safety as key secondary endpoints. Exploratory biomarker analyses are planned to explore mechanisms of response and resistance.

Who should consider this trial

Good fit: Adults (≥18) with HER2-positive advanced or metastatic breast cancer who progressed on prior trastuzumab deruxtecan, have measurable disease, ECOG 0–1, and adequate organ function are eligible.

Not a fit: Patients with prior exposure to RC48, active infections, a history of interstitial lung disease, uncontrolled comorbidities, or poor organ function are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combinations could provide new options that shrink tumors or delay progression for patients who no longer respond to T-Dxd.

How similar studies have performed: Early studies and real-world data have shown encouraging activity for RC48 and preclinical data support combining it with anti-angiogenic agents or HER family TKIs, but the specific post-T-Dxd combinations remain relatively untested in controlled trials.

Eligibility criteria

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.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wei Li, Ph.D

Conditions HER2 + Breast Cancer; Disitamab Vedotin; Bevacizumab; Pyrotinib; Trastuzumab deruxtecan failure