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

Prior treatment

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (at least once per month) within 14 days prior to enrollment.
• Weight loss ≥ 20% within 2 months prior to enrollment.
• Palliative radiotherapy within 14 days prior to enrollment.
• Prior anti-HER2 therapy.
• Major surgery within 28 days prior to enrollment, except for minimally invasive procedures such as peripherally inserted central catheter (PICC) placement.
  • Major surgery within 28 days prior to enrollment, except for minimally invasive procedures such as peripherally inserted central catheter (PICC) placement.
• Concurrent participation in another therapeutic clinical study.

Other illness

• Active autoimmune disease or history of autoimmune disease with potential for relapse. Patients with the following conditions are not excluded and may proceed to further screening
• Presence of other malignancies within the past 2 years or currently, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta, Tis, and T1).
• Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA \> 500 IU/mL, or patients positive for HCV RNA. Patients with inactive HBsAg carriers, those with hepatitis B who have been treated and are stable (HBV DNA \< 500 IU/mL), and those who have been cured of hepatitis C may be enrolled.
• Known allergy to any study drug or excipient.
• Any underlying medical condition, or alcohol/drug abuse or dependence, that in the investigator's opinion would interfere with study drug administration or affect the interpretation of drug toxicity or adverse events.

Other

• Known HER2-negative or HER2-low expression.

• 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.