DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer

DESTINY-Endometrial01 will investigate the efficacy of first-line T-DXd + rilvegostomig (Arm A) and/or T-DXd+ pembrolizumab (Arm B) when compared to chemotherapy (carboplatin + paclitaxel) + pembrolizumab (Arm C), by assessment of progression free survival (PFS), as assessed by BICR, in participants with HER2-expressing (IHC 3+/2+), pMMR, primary advanced (Stage III/IV) or recurrent EC.

• * Key Inclusion Criteria: * 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…

Use the source registry for the full inclusion and exclusion criteria before discussing referral or enrolment.