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

Official title

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

Overview

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.

Interventions

• Biological Trastuzumab+Serplulimab
  Patients will receive treatment with trastuzumab combined with serplulimab and chemotherapy. The treatment regimen is as follows: Trastuzumab: 6 mg/kg intravenously (IV) on day 1 of each 3-week cycle, with an initial loading dose of 8 mg/kg. Serplulimab: 4.5 mg/kg IV on day 1 of each 3-week cycle.

Primary outcome measures

• objective response rate (ORR) [Time frame: From the first dose of study treatment until disease progression, intolerance, or start of new anti-cancer therapy, assessed every 6 weeks for the first 12 months and every 12 weeks thereafter, up to approximately 24 months.]

Secondary outcome measures (2)

• Overall Survival (OS) [Time frame: From first dose until death, assessed every 6 weeks (Year 1) then every 12 weeks, and every 3 months during survival follow-up, up to approximately 24 months.]
• Progression-Free Survival (PFS) [Time frame: From the first dose of study treatment until disease progression, intolerance, or start of new anti-cancer therapy, assessed every 6 weeks for the first 12 months and every 12 weeks thereafter, up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• Known HER2-negative or HER2-low expression.
• 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).
• 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.
• 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.
• 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.

• 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.
• Concurrent participation in another therapeutic clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of China Medical University — Shenyang

Identifiers

NCT: NCT07506057 · CMU-HLX10-BTC/UC-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗