TQB2930 Injection for the Treatment of HER2-positive Advanced Breast Cancer

A Randomized, Open-label, Parallel-controlled, Multicenter Phase III Clinical Study Evaluating TQB2930 Combined With Investigator's Choice of Chemotherapy Versus Trastuzumab Combined With Investigator's Choice of Chemotherapy in the Treatment of HER2-Positive Advanced Breast Cancer

TQB2930 is a HER2 bispecific antibody drug. This study aims to evaluate the efficacy and safety of TQB2930 combined with investigator's choice of chemotherapy versus trastuzumab combined with investigator's choice of chemotherapy in subjects with HER2-positive advanced breast cancer who have received at least two prior lines of anti-HER2 therapy in the advanced station.

Inclusion Criteria:

• Subjects voluntarily participate in this study and sign the informed consent form;
• Age: 18-75 years (at time of signing Informed Consent Form (ICF); Eastern Cooperative Oncology Group (ECOG) performance status ≤1; estimated life expectancy >3 months;
• Cytologically or histologically confirmed Human Epidermal Growth Factor Receptor 2 (HER2)-positive recurrent or metastatic breast cancer;
• Received ≥2 prior lines of anti-HER2 targeted therapy in the advanced setting;
• At least one measurable lesion meeting Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) criteria (excluding brain lesions);
• Willing to receive one of the investigator-selected chemotherapy regimens;
• Adequate organ function;
• Female subjects of childbearing potential must agree to use effective contraception (e.g., Intrauterine Device (IUD), oral contraceptives, or condoms) during the study and for 6 months after study completion.

Exclusion Criteria:

• Concurrent Diseases and Medical History:

  • Other malignancies within 5 years before randomization or concurrent malignancies (except adequately treated non-melanoma skin cancer, in situ cervical cancer, or other cancers with curative treatment and no recurrence for ≥3 years);
  • Uncontrolled toxicities (>CTCAE Grade 1) from prior therapies (excluding alopecia);
  • Major surgery, open biopsy, or significant traumatic injury within 28 days before randomization;
  • Non-healing wounds or fractures;
  • Arterial/venous thromboembolic events within 6 months before randomization;
  • History of drug abuse or psychiatric disorders that may affect compliance;
  • Poorly controlled hypertension (e.g., Systolic Blood Pressure (SBP) >160 mmHg despite treatment);
  • ≥Grade 2 myocardial ischemia/infarction, arrhythmias, or congestive heart failure (New York Heart Association （NYHA）Class ≥II);
  • Active or uncontrolled severe infections (≥CTCAE Grade 2);
  • Known chronic hepatitis B;
  • Active syphilis infection;
  • Renal failure requiring hemodialysis/peritoneal dialysis;
  • Immunodeficiency disorders (e.g., Human Immunodeficiency Virus (HIV) ;
  • Poorly controlled diabetes;
  • Urine protein ≥++ on dipstick with 24-hour urine protein >1.0 g;
  • Epilepsy requiring medication.

• Tumor-Related Conditions and Treatments:

  • Chemotherapy, radiotherapy, or immunotherapy within 4 weeks before randomization (or within 5 half-lives of prior drugs, whichever is shorter);
  • Chinese herbal medicines with approved antitumor indications (per National Medical Products Administration (NMPA) labeling) within 2 weeks;
  • Severe Bone Lesions from bone metastases;
  • Untreated brain metastases, Leptomeningeal metastases, or carcinomatous meningitis;
  • Prior HER2-targeted therapy-induced Left Ventricular Ejection Fraction (LVEF) decline to <50% or absolute reduction >15%;
  • Uncontrolled or symptomatic Hypertension requiring ongoing bisphosphonates;
  • Uncontrolled cancer-related pain;
  • Existed Lymphangitis Carcinomatosa or uncontrolled effusions;
  • Use of Immunosuppressant or systemic corticosteroids (≥10 mg/day prednisone equivalent) within 2 weeks.

• Severe hypersensitivity to monoclonal antibodies;

• Participation in other antitumor clinical trials with investigational drugs within 4 weeks before randomization;

• Any condition deemed by the investigator to jeopardize subject safety or study completion.