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

• Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies are allowed except for sarcomas (carcinosarcomas are allowed).

• Following surgery or diagnostic biopsy, participant must have primary advanced disease (Stage III/IV) or first recurrent endometrial cancer and meet at least one of the following criteria:

∙ Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator's assessment.

‣ Primary Stage IV disease (per FIGO 2023) regardless of presence of measurable disease at baseline.

‣ First recurrent disease regardless of presence of measurable disease at baseline.

• Endometrial cancer with HER2 IHC expression of 3+ or 2+ as assessed by prospective central testing.

• Endometrial cancer that is determined pMMR by prospective central IHC testing.

• Provision of adequate FFPE tumor tissue sample of a tumor lesion that was not previously irradiated for central HER2, MMR, and PD-L1 IHC testing and valid central test results for randomization/ stratification.

• Prior therapy:

∙ Naïve to first-line systemic anticancer therapy. Participants may have received one prior line of adjuvant/neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if disease recurrence or progression occurred ≥ 6 months after last dose of chemotherapy. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed.

‣ No prior exposure to ADCs or immune checkpoint inhibitors including (but not limited to) anti-PD-1/PD-L1/PD-L2 and anti-CTLA-4 antibodies and therapeutic anticancer vaccines.

‣ Participants may have received prior radiation therapy for the treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Adequate treatment washout period is required.

• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.

• Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.

• Adequate organ and bone marrow function within 14 days before randomization.