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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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+.

Why it matters

Who can join: the full rules

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 it's running

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

Study contacts

• Study coordinator: Xiujuan Qu
• Email: qu_xiujuan@hotmail.com
• Phone: +8613604031355

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Trastuzumab Rezetecan with or without Adebrelimab for HER2-expressing advanced urothelial cancer

  This study will test whether Trastuzumab Rezetecan alone or combined with the immunotherapy Adebrelimab helps people with HER2-expressing locally advanced or metastatic urothelial cancer.

  Recruiting at 3 sites Phase 2 Sun Yat-sen University · Guangzhou, Guangdong and 5 other locations · NCT07241793

• Trastuzumab plus chemotherapy versus chemotherapy alone for first-line HER2-positive advanced biliary tract cancer

  This trial will test if adding trastuzumab to standard first-line chemotherapy helps people with HER2-positive advanced or metastatic biliary tract cancer control their disease longer than chemotherapy alone.

  Recruiting at 3 sites Phase 3 Tata Memorial Centre · Muzaffarpur, Bihar and 5 other locations · NCT07062263

• Evaluating MT-4561 in Patients with Advanced Solid Tumors

  This study is testing a new drug called MT-4561 to see if it is safe and effective for people with advanced solid tumors.

  Recruiting at 6 sites Phase 1/2 Tanabe Pharma America, Inc. · Los Angeles, California and 5 other locations · NCT06943521

• Testing ZM008 alone and with Pembrolizumab in patients with advanced solid tumors

  This study is testing a new treatment called ZM008, alone and with another drug called Pembrolizumab, to see if it can help patients with advanced solid tumors who have run out of other treatment options.

  Recruiting at 3 sites Phase 1 Zumutor Biologics Inc. · Boston, Massachusetts and 2 other locations · NCT06451497

• Evaluating BL-M07D1 for HER2 Expressing Solid Tumors

  This study is testing a new treatment called BL-M07D1 to see if it is safe and effective for people with advanced solid tumors that have a specific protein called HER2 after they have tried other treatments.

  Recruiting at 24 sites Phase 1 SystImmune Inc. · Birmingham, Alabama and 25 other locations · NCT06293898

• Neoadjuvant trastuzumab, durvalumab, and FLOT for HER2-positive gastric or GEJ cancer

  This study tests a pre-surgery treatment combining trastuzumab, durvalumab, and FLOT for patients with HER2-positive locally advanced gastric or gastroesophageal junction cancer to see how many achieve complete tumor disappearance.

  Recruiting Phase 2 Samsung Medical Center · Seoul, Gang-Nam · NCT07911280

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.