Zanidatamab Combined With Liposomal Irinotecan and Capecitabine for Second-line Treatment of HER2-positive Unresectable Biliary Tract Tumors

NCT07841873 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 2026KY1293
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, single-arm, phase II clinical study designed to explore the efficacy and safety of zanidatamab in combination with liposomal irinotecan and capecitabine as second-line therapy for HER2-positive advanced biliary tract cancer. Fifteen patients with unresectable locally advanced or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer, will be enrolled after progression on or intolerance to first-line therapy. HER2 positivity must be confirmed by immunohistochemistry and/or fluorescence in situ hybridization, defined as IHC 3+ or IHC 2+ with FISH-confirmed amplification. Zanidatamab 20 mg/kg will be administered intravenously on Day 1 every 2 weeks; liposomal irinotecan 50 mg/m² will be administered intravenously over 90 minutes on Day 2 every 2 weeks; and capecitabine 1,000 mg/m² will be administered orally twice daily on Days 1-10 of each 14-day cycle. Chemotherapy will be administered for a maximum of six cycles, and study treatment will continue until disease progression or unacceptable toxicity. The primary endpoint is objective response rate, as assessed according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, and safety.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate as assessed by RECIST v 1.1

  24 months

Secondary Outcomes (5)

• Disease control rate as assessed by RECIST v1.1

  24 months

• duration of response as assessed by RECIST v1.1

  24 months

• progression-free survival as assessed by RECIST v1.1

  24 months

• overall survival

  48 months

• Adverse Events as Assessed by CTCAE v5.0

  24 months

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Zanidatamab

Interventions

Zanidatamab DRUG

Zanidatamab 20 mg/kg will be administered intravenously on Day 1 every 2 weeks; liposomal irinotecan 50 mg/m² will be administered intravenously on Day 2 every 2 weeks; and capecitabine 1,000 mg/m² will be administered orally twice daily on Days 1-10 of each 14-day cycle. Chemotherapy will be administered for a maximum of six cycles, and study treatment will continue until disease progression or unacceptable toxicity.

Also known as: liposomal irinotecan, capecitabine

Treatment

Eligibility Criteria

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

You may qualify if:

• Informed consent: Voluntary provision of written informed consent; age ≥18 years.
• Pathologic diagnosis: Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer.
• HER2 status: HER2 positivity confirmed by immunohistochemistry and/or fluorescence in situ hybridization, defined as IHC 3+ or IHC 2+ with FISH-confirmed amplification. Local test results from each participating center will be used for eligibility screening.
• Prior treatment:
• Disease progression after or intolerance to a standard first-line regimen containing a programmed cell death protein 1 or programmed death-ligand 1 inhibitor.
• No prior treatment with irinotecan, capecitabine, or any HER2-targeted therapy.
• Measurable disease: At least one measurable target lesion according to RECIST version 1.1.
• Performance status: Eastern Cooperative Oncology Group performance status of 0 or 1.
• Life expectancy: ≥12 weeks.
• Adequate organ function, based on test results obtained within 14 days before the first dose:
• Hematologic function: Absolute neutrophil count ≥1.5 × 10⁹/L; hemoglobin ≥90 g/L; platelet count ≥100 × 10⁹/L.
• Hepatic function: Total bilirubin ≤1.5 × the upper limit of normal; alanine aminotransferase and aspartate aminotransferase ≤2.5 × the upper limit of normal, or ≤5 × the upper limit of normal in patients with liver metastases.
• Renal function: Serum creatinine ≤1.5 × the upper limit of normal or creatinine clearance ≥30 mL/min.
• Cardiac function: Left ventricular ejection fraction ≥50%.
• Coagulation function: International normalized ratio ≤1.5 × the upper limit of normal.

You may not qualify if:

• History of malignancy: Another active malignancy within the previous 5 years, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin.
• Tumor type: Ampullary carcinoma.
• Uncontrolled conditions:
• Uncontrolled pleural effusion, ascites, or pericardial effusion. Patients requiring drainage only may be enrolled if there is no clinically significant reaccumulation within 3 days after drainage is discontinued.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Recent treatment:
• Major surgery or radiotherapy within 4 weeks before the first dose.
• Traditional Chinese medicines with an approved antitumor indication within 2 weeks before the first dose.
• Participation in another interventional clinical study within 4 weeks before the first dose.
• Comorbidities:
• A history of myocardial infarction or unstable angina within 6 months before enrollment; troponin levels meeting diagnostic criteria for myocardial infarction; or clinically significant cardiac disease, including ventricular arrhythmias requiring treatment, uncontrolled hypertension, or any history of symptomatic heart failure.
• Active infection, including hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection.
• Patients positive for hepatitis B surface antigen must have an HBV DNA level \<1,000 IU/mL and agree to receive antiviral therapy throughout the study.
• Hepatitis C virus infection, except that the following patients are eligible: (i) patients with no history of curative antiviral therapy who have a confirmed negative viral load; or (ii) patients who completed curative antiviral therapy ≥12 weeks before enrollment and have a negative viral load.
• Gastrointestinal conditions: Factors that may affect absorption of oral medication, such as chronic diarrhea or intestinal obstruction; or Grade ≥2 diarrhea.

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

zanidatamab; irinotecan sucrosofate; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

gang wang

CONTACT

+8613855196707; wanggang829@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 20, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): November 30, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share