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

Required: HER2 (ERBB2) IHC 3+ (IHC 3+)

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

Required: HER2 (ERBB2) IHC 2+ (IHC 2+)

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

Required: MMR proficient (pMMR)

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

Must have received: chemotherapy — adjuvant/neoadjuvant

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.

Must have received: radiation therapy

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.

Cannot have received: antibody-drug conjugate

No prior exposure to ADCs

Cannot have received: checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4)

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

Cannot have received: therapeutic anticancer vaccine

No prior exposure to ... therapeutic anticancer vaccines.