An Open-label, Single-arm Phase II Clinical Study of Trastuzumab in Combination With Serplulimab and Chemotherapy for the Treatment of HER2-overexpressing Unresectable Locally Advanced or Metastatic Biliary Tract Cancer or Urothelial Carcinoma After Failure of Standard Therapy
his single-center phase II clinical study enrolls patients with unresectable locally advanced or metastatic HER2-overexpressing biliary tract cancer or urothelial carcinoma who have failed standard treatment. Participants receive trastuzumab in combination with serplulimab and chemotherapy. The study aims to evaluate the efficacy and safety of this regimen in this patient population. The primary endpoint is objective response rate (ORR). Secondary endpoints include overall survival (OS), progression-free survival (PFS), and safety.
• Age 18 to 75 years, male or female.
• Histologically or cytologically confirmed recurrent and/or metastatic advanced biliary tract cancer or urothelial carcinoma.
• Disease progression after at least one prior line of systemic antitumor therapy. For patients who received systemic antitumor therapy during adjuvant therapy or concurrent chemoradiotherapy, progression occurring within 6 months after completion of therapy is considered as one prior line of therapy.
• HER2 overexpression confirmed by immunohistochemistry (IHC) 3+ or IHC 2+ with in situ hybridization (ISH)+.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• No prior anti-HER2 therapy.
• At least one measurable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ reserve function:
• Urine protein ≤ 1+ on urinalysis or 24-hour urine protein \< 1.0 g, and albumin \> 2.7 g/dL.
• Life expectancy ≥ 3 months as judged by the investigator.
• Ability to provide written informed consent and understand and agree to comply with study requirements and assessment schedule.
• Female patients of childbearing potential must agree to use highly effective contraception during the treatment period and for 12 weeks after the last dose; male patients must agree to use highly effective contraception during the treatment period and for 6 months after the last dose.