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 (SHIELD)

March 26, 2026 updated by: Xiujuan Qu

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Liaoning
      • Shenyang, Liaoning, China, 110001
        • Recruiting
        • The First Affiliated Hospital of China Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental group

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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The time from the first dose of study treatment to the first documented disease progression or death from any cause.
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
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.
The time from randomization (or first dose) to death from any cause.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xiujuan Qu

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2025

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

March 26, 2026

First Submitted That Met QC Criteria

March 26, 2026

First Posted (Actual)

April 1, 2026

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMU-HLX10-BTC/UC-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The study involves sensitive patient information and complex multi - omics data. Sharing IPD could risk patient privacy and requires substantial resources to manage properly. However, we're open to future collaborations to potentially share findings in a controlled manner.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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