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

Key Inclusion Criteria:

• Participants must be ≥ 18 years of age at the time of screening. Other agerestrictions may apply as per local regulations;

• Male and female;

• Unresectable, previously untreated, locally advanced or metastatic BTC. Priortreatment in the perioperative and/or adjuvant setting is permissible provided thereis > 6 months (180 days) between the end of adjuvant treatment and the diagnosis oflocally 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 ofchildbearing potential;

Key Exclusion Criteria:

• Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitorsand therapeutic anticancer vaccines;

• histologically confirmed ampullary carcinoma;

• history of substance abuse or any other medical conditions such as clinicallysignificant cardiac or psychological conditions;

• spinal cord compression or clinically active central nervous system metastases,defined as untreated and symptomatic, or requiring therapy with corticosteroids oranticonvulsants to control associated symptoms;

• medical history of myocardial infarction within 6 months beforerandomization/enrollment, symptomatic congestive heart failure (New York HeartAssociation Class II to IV), unstable angina pectoris, clinically important cardiacarrhythmias, or a recent (< 6 months) cardiovascular event including stroke;

• Serious chronic gastrointestinal conditions associated with diarrhea (eg, activeinflammatory bowel disease); active non-infectious skin disease (including any graderash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment;

• active autoimmune, connective tissue or inflammatory disorders that has requiredsystemic treatment in the past 2 years, or where there is documented, or a suspicionof 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 wheresuspected ILD/pneumonitis cannot be ruled out by imaging at screening;

• Lung-specific intercurrent clinically significant illnesses including, but notlimited 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 becomepregnant;

• Participation in another clinical study with a study intervention or investigationalmedicinal device administered in the last 6 months prior to randomization, orconcurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of aninterventional study (only randomized portion).