Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01)

Key Inclusion Criteria:

1. Sign and date the tissue prescreening informed consent form (ICF), prior to HER2central testing. Sign and date the main ICF, prior to the start of any trial-specific qualification procedures. Consent to optional PGx prior to any PGxprocedures. For participants in the safety run-in phase, a safety run-in ICF needsto be signed and dated prior to the start of any trial-specific qualificationprocedures.

2. Adults ≥18 years of age on the day of signing the ICF. Follow local regulatoryrequirements if the legal age of consent for trial participation is >18 years old.

3. Has histologically confirmed diagnosis of epithelial high-grade ovarian, fallopiantube or primary peritoneal carcinoma (including but not limiting to serous,endometrioid, clear cell, carcinosarcoma, mucinous).

4. Is newly diagnosed FIGO Stage III or IV.

5. Has HER2 expression per 2016 ASCO-CAP gastric cancer IHC scoring (3+/2+/1+)guidelines1 by prospective central testing. For participants in the safety run-inphase, HER2 expression assessed by either local (require using ASCO-CAP gastriccancer IHC scoring [IHC 3+/2+/1+] guidelines) or central assessment (if available)is acceptable. Submission of the pathology report is required for participantsenrolled based on local HER2 IHC results.

6. Has adequate tumor tissue sample available for assessment of HER2 by centrallaboratory. Tumor tissue block or sufficient tissue slides are required for HER2testing and retrospective HRD status determination. Participants in the safetyrun-in phase who are enrolled based on local HER2 IHC results are recommended toprovide tumor tissue sample from the same specimen for central assessment.

7. Has a local HRD or breast cancer gene (BRCA) test result available. Participantswith BRCA wildtype will have a local HRD test results, as applicable.

8. Has received standard of care bevacizumab in combination with front line platinumbased chemotherapy as per approved indication and clinical guidelines and iseligible to continue single agent bevacizumab maintenance per standard of care andinvestigator discretion.

Key Exclusion Criteria:

1. Has ovarian, fallopian tube, or peritoneal cancer of non-epithelial origin.

2. Has a BRCA mutation as per local test.

3. Participant to receive PARP inhibitor as maintenance per standard of care andinvestigator discretion. Reasons for which the participant is not eligible for PARPinhibitor will be recorded in the eCRF as follows: HRD negative HRD positive with SDas best response after platinum HRD positive non-serous histology HRD tested, butinconclusive HRD positive but safety concern (safety concern to be specified).

4. Has a history of severe hypersensitivity reactions to either the drug substances orinactive ingredients in the drug products and other monoclonal antibodies.

5. Previous Cerebral-Vascular Accident, Transient Ischemic Attack or Sub- ArachnoidsHemorrhage within 6 months prior to randomization.

6. Has evidence of bleeding diathesis or significant coagulopathy (in the absence ofanticoagulation therapy).

7. Has a history of hemorrhagic disorders, abdominal fistula, gastrointestinalperforation, or active gastrointestinal bleeding within 6 months beforerandomization.

8. Evidence of active or ongoing bowel obstruction.

9. Has lung-specific intercurrent clinically significant illnesses including, but notlimited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 monthsof the trial randomization, severe asthma, severe chronic obstructive pulmonarydisease, restrictive lung disease, pleural effusion, pneumonectomy, etc.)

10. Has a history of (non-infectious) ILD/pneumonitis that required steroids, hascurrent ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out byimaging at Screening.

11. Clinically severe pulmonary compromise resulting from intercurrent pulmonaryillnesses including, but not limited to, any underlying pulmonary disorder (iepulmonary emboli within three months of the trial enrollment, severe asthma, severeCOPD, restrictive lung disease, pleural effusion etc.), and any autoimmune,connective tissue or inflammatory disorders with potential pulmonary involvement (ieRheumatoid arthritis, Sjogren's, sarcoidosis etc.), or prior pneumonectomy.