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 ICF, prior to HER2 central testing. Sign anddate the Main ICF, prior to the start of any trial- specific qualificationprocedures. Consent to optional PGx prior to any PGx procedures.

*For participants in the safety run-in phase, a safety run-in ICF needs to be signedand dated prior to the start of any trial-specific qualification procedures.

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 per local assessment (including but notlimiting 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-in phase, HER2 expression assessed by eitherlocal (require using ASCO-CAP gastric cancer IHC scoring [IHC 3+/2+/1+] guidelines)or central assessment (if available) is acceptable. Submission of the pathologyreport is required for participants enrolled 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 safety run-in phase who are enrolled based on local HER2 IHCresults are recommended to provide tumor tissue sample from the same specimen forcentral assessment.

7. Has a local HRD or BRCA test result available. Participants with BRCA-wildtype willhave a local HRD test results, as applicable.

8. Has received up to 6 cycles of standard of care bevacizumab in combination withfrontline platinum- based chemotherapy as per approved indication and clinicalguidelines and is eligible to continue single agent bevacizumab maintenance perstandard of care and investigator discretion.

Key Exclusion Criteria:

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

2. Has a known or suspected deleterious BRCA alteration as per local test that makesthe patient eligible for PARP inhibitor.

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 SD as best response after platinum

• HRD positive non-serous histology Note: For participants enrolled from theRepublic of Korea

• HRD tested, but inconclusive

• 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.

*Note: For participants enrolled from the Republic of Korea,

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 a medical history of myocardial infarction within 6 months before randomization,symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (asdefined by the manufacturer), and without any myocardial infarction related symptomsshould have a cardiologic consultation during the Screening Period to rule outmyocardial infarction.

10. Has a corrected QT interval prolongation to >480 msec based on average of theScreening triplicate 12-lead ECG.

11. 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.