• 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.