• 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;