RC48 Combined With Chemotherapy in HER2-Positive Advanced Breast Cancer Patients With Prior TOP1i-ADC Failure

NCT07366840 | Not Yet Recruiting Phase 2

• 1 other identifier: 2510331-7
• Study Type: interventional
• Target: 268
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the safety and efficacy of RC48 (a HER2 antibody drug conjugate with MMAE payload) in combination with gemcitabine or capecitabine (with or without trastuzumab/inetetamab), for treatment of patients with HER2-positive advanced breast cancer (ABC) who have developed disease progression or intolerance to prior therapy with a topoisomerase I inhibitor antibody-drug conjugate (TOP1i-ADC).

Conditions

HER2-positive Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Median progression free survival (by investigator)

  Progression-Free Survival (PFS), analyzed using the Kaplan-Meier method, is defined as the time from randomization to the first occurrence of disease progression or death, whichever comes first. For subjects without evidence of disease progression or death at the time of analysis, data will be censored at the date of their last tumor assessment.

  The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.

Secondary Outcomes (5)

• Objective Response Rate (by investigator)

  Baseline at screening and the time of the identification of disease progression, assessed up to 36 months.

• Median overall survival (by investigator)

  The observation period for this endpoint will be terminated upon death or if disease progression occurs after 1 year of follow-up.

• Duration of response (by investigator)

  The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.

• Disease control rate (by investigator)

  The observation period for this endpoint is up to 36 months, and will be terminated early upon disease progression or death.

• Adverse events

  The observation period for this endpoint is up to 36 months.

Study Arms (2)

Disitamab Vedotin plus chemo

EXPERIMENTAL

Participants received Disitamab Vedotin (RC48), 2.0mg/kg intravenously on day 1 of two-week cycle, plus chemotherapy of physician's choice (gemcitabine 1000mg/m2, intravenously on days 1 and 8 of 21-day cycle, or capecitabine, 1000 mg/m2, orally twice daily on days 1-14 of 21-day cycle), with or without guideline-recommended anti-HER2 monoclonal antibody (Trastuzumab or Inetetamab (an analog of trastuzumab), 8 mg/kg loading dose, intravenously, then 6 mg/kg without loading dose, on day 1 of 21-day cycle) until physician's verified progression or unacceptable toxicity.

Drug: Disitamab Vedotin; Drug: Gemcitabine; Drug: Capecitabine; Drug: Inetetamab

Trastuzumab plus chemo

EXPERIMENTAL

Participants received chemotherapy of physician's choice (gemcitabine 1000mg/m2, intravenously on days 1 and 8 of 21-day cycle, or capecitabine, 1000mg/m2, orally twice daily on days 1-14 of 21-day cycle), with or without guideline-recommended anti-HER2 monoclonal antibody (Trastuzumab or Inetetamab (an analog of trastuzumab), 8 mg/kg loading dose, intravenously, then 6 mg/kg without loading dose, on day 1 of 21-day cycle) until physician's verified progression or unacceptable toxicity.

Drug: Gemcitabine; Drug: Capecitabine; Drug: Trastuzumab; Drug: Inetetamab

Interventions

Disitamab Vedotin DRUG

2.0mg/kg every two weeks

Also known as: RC48

Disitamab Vedotin plus chemo

Gemcitabine DRUG

1000mg/m2 on days 1 and 8 every three weeks

Disitamab Vedotin plus chemo; Trastuzumab plus chemo

Capecitabine DRUG

1000 mg/m2 twice daily on days 1 to14 every three weeks

Disitamab Vedotin plus chemo; Trastuzumab plus chemo

Trastuzumab DRUG

6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg

Trastuzumab plus chemo

Inetetamab DRUG

6 mg/kg once every three weeks, with an initial loading dose of 8 mg/kg

Disitamab Vedotin plus chemo; Trastuzumab plus chemo

Eligibility Criteria

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

You may qualify if:

• Female subjects aged ≥ 18 years.
• Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+ with positive FISH) advanced breast cancer.
• Disease progression on or intolerance to prior treatment with a topoisomerase I inhibitor-conjugated antibody-drug conjugate (TOP1i-ADC).
• ≤ 3 lines of systemic therapy received in the recurrent or metastatic setting. Prior exposure to only one ADC agent.
• At least one extracranial measurable lesion according to RECIST v1.1 criteria.
• ECOG Performance Status (PS) of 0 or 1.
• Adequate function of major organs, meeting the following criteria:Hematological criteria:Hemoglobin (HB) ≥ 90 g/L (no blood transfusion within 14 days prior);Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L;Platelet count (PLT) ≥ 75 × 10⁹/L.Biochemical criteria:Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN; for subjects with liver metastases, ALT and AST ≤ 5 × ULN;Serum Creatinine (Cr) ≤ 1 × ULN, and calculated Creatinine Clearance Rate (Ccr) \> 50 mL/min (using the Cockcroft-Gault formula).
• Expected survival ≥ 3 months.
• No prior radiotherapy, chemotherapy, endocrine therapy, molecular targeted therapy or surgery within 3 weeks prior to the start of the study; complete recovery from acute toxicities of previous treatments (if surgery was performed, surgical wounds must be fully healed); no peripheral neuropathy or peripheral neurotoxicity of Grade 1 at most.
• Female subjects with childbearing potential must use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last administration of the study drug.
• Voluntary participation in the study, provision of written informed consent, and good compliance with study procedures and follow-up schedules.

You may not qualify if:

• Unstable brain metastases, leptomeningeal metastases, or untreated brain metastases (excluding subjects with treated and stable brain metastases who have been asymptomatic for ≥ 4 weeks).
• A history of arterial or venous thromboembolic events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 3 years prior to the start of study treatment.
• Uncontrolled systemic diseases, including diabetes mellitus, hypertension, pulmonary fibrosis, acute lung disease, liver cirrhosis, etc.
• Current active infection requiring systemic treatment.
• Failure to recover from toxicities of prior anti-tumor therapy to CTCAE v5.0 Grade 0 or 1 (except for alopecia, hyperpigmentation, or other conditions deemed by the investigator not to increase the risk of study drug administration).
• A history of clinically significant or uncontrolled cardiac diseases, including severe ventricular arrhythmia, congestive heart failure, angina pectoris, or myocardial infarction within 6 months prior.
• Known immediate or delayed hypersensitivity to RC48 or any of its components.
• Pregnant or lactating women.
• A history of other malignancies within 3 years prior (except for bilateral breast cancer with HER2 positivity in both lesions, cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, papillary thyroid carcinoma with favorable prognosis, or carcinoma in situ of the lung or minimally invasive adenocarcinoma with favorable prognosis).
• Any other conditions that, in the investigator's judgment, make the subject unsuitable for participation in the study.

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

disitamab vedotin; Gemcitabine; Capecitabine; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jian Zhang, MD

CONTACT

+8664175590; syner2000@163.com

Yanchun Meng, MD

CONTACT

+8664175590; ycmclinicaltrials@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: January 14, 2026
• First Posted: January 26, 2026
• Study Start: January 16, 2026
• Primary Completion (Estimated): January 16, 2028
• Study Completion (Estimated): January 16, 2029
• Last Updated: January 26, 2026

Record last verified: 2026-01