Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Key Inclusion Criteria:
* Participants must be ≥ 18 years of age at the time of screening. Other age restrictions may apply as per local regulations;
* Male and female;
* Unresectable, previously untreated, locally advanced or metastatic BTC. Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is \> 6 months (180 days) between the end of adjuvant treatment and the diagnosis of locally advanced or metastatic disease.
* histologically confirmed HER2-expressing (IHC 3+ or IHC 2+) BTC;
* Provision of FFPE tumor sample that is no older than 3 years;
* At least one target lesion assessed by the Investigator based on RECIST v1.1 (randomized portion only);
* WHO/ECOG performance status of 0 or 1;
* Adequate organ and bone marrow function within 14 days before randomization;
* Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential;
Key Exclusion Criteria:
* Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines;
* histologically confirmed ampullary carcinoma;
* history of substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions;
* spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms;
* medical history of myocardial infarction within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke;
* Serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease); active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment;
* active autoimmune, connective tissue or inflammatory disorders that has required systemic treatment in the past 2 years, or where there is documented, or a suspicion of pulmonary involvement at the time of screening;
* Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG;
* History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening;
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder;
* Prior pneumonectomy (complete);
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals;
* Active primary immunodeficiency, known uncontrolled active HIV infection or HCV;
* Pregnant or breastfeeding female patients, or patients who are planning to become pregnant;
* Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 6 months prior to randomization, or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study (only randomized portion).
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 6/18/2025. Questions regarding updates should be directed to the study team contact.