Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.

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Key information

Conditions

Biliary Tract Cancer Adenocarcinoma Biliary Tract Diseases Biliary Tract Neoplasms Carcinoma Cholangiocarcinoma Digestive System Diseases Digestive System Neoplasms Gallbladder Diseases Gallbladder Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires (caba), Buenos Altes, Argentina

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Histologically- or cytologically-confirmed Biliary Tract Cancer (BTC), including Gallbladder Cancer (GBC), Intrahepatic Cholangiocarcinoma (ICC), or Extrahepatic Cholangiocarcinoma (ECC).
Locally advanced unresectable or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
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.
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.
Assessable (measurable or non-measurable) disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), per investigator assessment.
Male or female ≥ 18 years or age (or the legal age of adulthood per country-specific regulations).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate organ function
Females of childbearing potential must have a negative pregnancy test result.
Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion criteria

Prior treatment with a HER2-targeted agent
Prior treatment with checkpoint inhibitors, other than durvalumab or pembrolizumab
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.
Use of systemic corticosteroids.
Brain metastases
Severe chronic or active infections
History of allogeneic organ transplantation.
Active or prior autoimmune inflammatory conditions
History of interstitial lung disease or non-infectious pneumonitis.
Participation in another clinical trial with an investigational medicinal product within the last 3 months.
Females who are breastfeeding
Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
Use of phenytoin