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Zanidatamab combined with standard therapy for advanced HER2-positive biliary tract cancer

An Open-label Randomized Trial of the Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy Alone for Advanced HER2-positive Biliary Tract Cancer

Phase 3 Interventional Jazz Pharmaceuticals · NCT06282575

This study is testing if a new treatment combining Zanidatamab with standard chemotherapy can help people with advanced HER2-positive biliary tract cancer feel better and live longer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment286 (estimated)
Ages18 Years and up
SexAll
SponsorJazz Pharmaceuticals Industry-sponsored
Drugs / interventionsdurvalumab, pembrolizumab, Zanidatamab
Locations185 sites (Duarte, California and 184 other locations)
Trial IDNCT06282575 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of Zanidatamab in combination with Cisplatin and Gemcitabine, with the option of adding a PD-1/L1 inhibitor, as a first-line treatment for patients with advanced HER2-positive biliary tract cancer. Participants must have histologically confirmed biliary tract cancer that is locally advanced or metastatic and not eligible for curative treatments. The study aims to determine if this combination therapy improves outcomes compared to standard care alone.

Who should consider this trial

Good fit: Ideal candidates include individuals with HER2-positive biliary tract cancer who are not eligible for curative resection and have received limited prior systemic therapy.

Not a fit: Patients with HER2-negative biliary tract cancer or those who have received more than two cycles of prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced HER2-positive biliary tract cancer.

How similar studies have performed: Other studies have shown promising results with similar HER2-targeted therapies in various cancers, suggesting potential success for this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria

1. Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
2. Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
3. Received no more than 2 cycles of systemic therapy which is limited to Cisplatin and Gemcitabine (CisGem) with or without a PD-1/L1 inhibitor (physician's choice of durvalumab or pembrolizumab, where approved under local regulations) for advanced unresectable or metastatic disease.
4. HER2-positive disease (defined as IHC 3+; or IHC 2+/ ISH+) by IHC and in situ Hybridization (ISH) assay (in participants with IHC 2+ tumors) at a central laboratory on new biopsy tissue or archival tissue from the most recent biopsy.
5. Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
6. Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Adequate organ function
9. Females of childbearing potential must have a negative pregnancy test result.
10. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion Criteria

1. Prior treatment with a HER2-targeted agent
2. Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
3. The following BTC histologic subtypes are excluded: small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology, and mucinous cystic neoplasms detected in the biliary tract region.
4. Use of systemic corticosteroids.
5. Brain metastases
6. Severe chronic or active infections
7. History of allogeneic organ transplantation.
8. Active or prior autoimmune inflammatory conditions
9. History of interstitial lung disease or non-infectious pneumonitis.
10. Participation in another clinical trial with an investigational medicinal product within the last 3 months.
11. Females who are breastfeeding
12. Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
13. Use of phenytoin

Where this trial is running

Duarte, California and 184 other locations

+135 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Biliary Tract CancerJZP598ZW25HER-2 positive BIliary Tract cancerGallbladder CancerIntrahepatic CholangiocarcinomaExtrahepatic CholangiocarcinomaZanidatamab
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.