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

NCT07506057 | Recruiting Phase 2

• 1 other identifier: CMU-HLX10-BTC/UC-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urothelial Carcinoma; Biliary Tract Cancer; HER2

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  Objective response rate (ORR) as assessed by the investigator according to RECIST version 1.1, defined as the proportion of patients achieving complete response (CR) or partial response (PR).

  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 Outcomes (2)

• Overall Survival (OS)

  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)

  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

Study Arms (1)

Experimental group

EXPERIMENTAL

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. Chemotherapy for Biliary Tract Cancer: Selected by the investigator based on the participant's condition, including but not limited to the FOLFOX regimen: oxaliplatin 85 mg/m² IV over 2 hours on day 1, leucovorin 400 mg/m² IV over 2 hours on day 1, fluorouracil 400 mg/m² IV bolus on day 1, followed by fluorouracil 2400-3000 mg/m² continuous IV infusion over 46 hours on day 1, repeated every 2 weeks. Chemotherapy for Urothelial Carcinoma: Selected by the investigator based on the participant's condition, including but not limited to paclitaxel 135-175 mg/m² IV on day 1, repeated every 3 weeks.

Biological: Trastuzumab+Serplulimab

Interventions

Trastuzumab+Serplulimab BIOLOGICAL

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.

Experimental group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xiujuan Qu: lead

Study Sites (1)

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, 110001, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases

Central Study Contacts

Xiujuan Qu

CONTACT

+8613604031355; qu_xiujuan@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Oncology

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 1, 2026
• Study Start: July 15, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)