Trastuzumab plus serplulimab with chemotherapy for HER2-positive advanced biliary tract or urothelial cancer after prior therapy

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

This study will test whether adding trastuzumab and serplulimab to chemotherapy helps people with HER2-positive unresectable or metastatic biliary tract cancer or urothelial carcinoma who have not responded to standard treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: China Medical University, China (Academic / other)
• Drugs / interventions: trastuzumab, serplulimab, chemotherapy
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT07506057 on ClinicalTrials.gov

What this trial studies

This single-center phase II trial enrolls adults 18–75 with unresectable locally advanced or metastatic HER2-overexpressing biliary tract cancer or urothelial carcinoma who progressed after at least one line of systemic therapy. Participants receive a combination of trastuzumab (anti-HER2), serplulimab (anti–PD-1), and chemotherapy, with measurable disease required by RECIST 1.1 and LVEF ≥50%. The primary endpoint is objective response rate (ORR), and secondary endpoints include overall survival (OS), progression-free survival (PFS), and safety. Patients with prior anti-HER2 therapy are excluded, and HER2 status must be IHC 3+ or IHC 2+ with ISH+.

Who should consider this trial

Good fit: Adults aged 18–75 with unresectable locally advanced or metastatic biliary tract cancer or urothelial carcinoma that overexpresses HER2 (IHC 3+ or IHC 2+ with ISH+), who progressed after at least one prior systemic therapy, have ECOG 0–1, measurable disease, and LVEF ≥50%.

Not a fit: Patients without HER2 overexpression, those who have already received anti-HER2 therapy, or those who are too frail or have poor cardiac function or other disqualifying conditions are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could shrink tumors and extend survival for patients with HER2-overexpressing advanced biliary tract or urothelial cancers who have exhausted standard options.

How similar studies have performed: Combining HER2-targeted therapy with PD-1 blockade has shown promising signals in some HER2-positive cancers, but high-quality evidence in biliary tract and urothelial cancer remains limited.

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.

Where this trial is running

Shenyang, Liaoning

• The First Affiliated Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Study coordinator: Xiujuan Qu

Conditions Urothelial Carcinoma; Biliary Tract Cancer; HER2