Endometrial Cancer Clinical Trials

• ≥ 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).

• Participant must have primary advanced disease (Stage III/IV) or 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 (per FIGO 2023) disease regardless of presence of measurable disease at baseline.

⁃ Recurrent disease regardless of presence of measurable disease at baseline.

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

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

• Provision of an adequate FFPE tumor tissue sample for central HER2, MMR, and PD-L1 IHC testing.

• Prior therapy:

‣ No prior chemotherapy for the treatment of EC, except for one prior line of adjuvant/ neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if completed ≥ 6 months prior to signature of the main ICF. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed.

⁃ No prior exposure to antibody-drug conjugates or immune checkpoint inhibitors

⁃ Participants may have received prior radiation therapy for the treatment of endometrial cancer. Adequate treatment washout period is required

⁃ Participants may have received prior hormonal therapy for the treatment of endometrial cancer. Adequate treatment washout period is required

• ECOG 0-1.

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

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

• The participant is not considered a candidate for curative therapy in the judgment of the investigator.