Phase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer

Eligibility 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;
• * 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).