A Study of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab as Maintenance Therapy in Second-Line Platinum-Sensitive Recurrent Ovarian Cancer (REJOICE-Ovarian03)

1. Adult participants with assigned female sex at birth.
2. Participants with histologically or cytologically documented high-grade (Grade 3) serous or endometrioid epithelial ovarian cancer (OVC), primary peritoneal cancer, or fallopian tube cancer.
3. Has an homologous recombinant deficiency (HRD) or breast cancer gene (BRCA) test result using a validated or approved test as per applicable regulations available.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
5. Required baseline local laboratory data (within 7 days prior to randomization) as specified in the protocol.
6. A woman of childbearing potential (WOCBP), as specified in the protocol, is eligible to participate if the protocol-specified conditions are met.

7. Must have received 2 prior lines of platinum-based therapy:

   • For the first-line (1L) platinum-based chemotherapy (penultimate, platinum-based course prior to enrollment on the trial), must have platinum-sensitive disease after this treatment, defined as documented radiologic disease progression assessed by the investigator (evident measurable or non-measurable disease according to RECIST v1.1) >6 months following the last dose of the platinum administered.
   • For the second (last) platinum-based chemotherapy course prior to enrollment on the trial, must have received a platinum-containing regimen for a minimum of 4 cycles and a maximum of 8 cycles.
8. Must have achieved evidence of non-progressive radiological disease based on investigator-assessed RECIST 1.1 and CA-125 at the end of induction treatment with platinum-based doublet chemotherapy (no evidence of disease [NED], complete response [CR], partial response [PR] or stable disease [SD] for participants with measurable disease at baseline; or NED, CR, or non-CR/non-progressive disease [PD] for participants with non-measurable disease based on RECIST v1.1).
9. According to investigator assessment, polymerase inhibitor (PARPi) as 2L maintenance treatment is not the preferred option for the participant.
10. Must be randomized between 4 and 9 weeks after completion of their final dose of the platinum-containing regimen.
11. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other trial procedures, and trial restrictions.

Exclusion Criteria:

1. Non-serous or non-endometrioid high-grade epithelial histology, or non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e., germ cell tumors) or low-grade/borderline OVC.

2. Inadequate washout period before randomization, defined as follows:

   • Major surgery less than (\<)28 days.
   • Radiation therapy less than equal to (≤)28 days (if palliative stereotactic radiation therapy without abdominal radiation, ≤14 days).
   • Systemic anticancer therapy (including but not limited to antibody-drug therapy, retinoid therapy, and hormonal therapy) \<28 days or 5 half-lives, whichever is shorter, before starting trial intervention or current participation in other therapeutic investigational procedures.
   • Chloroquine/hydroxychloroquine ≤14 days.
   • Exposure to another investigational trial intervention within 28 days prior to start of trial intervention or current participation in other therapeutic investigational procedures.
3. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with untreated and asymptomatic brain metastases or participants with previously treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the trial if they have recovered from the acute toxic effect of radiotherapy, at the investigator's discretion. A minimum of 2 weeks must have elapsed between the end of radiotherapy and trial intervention and there should be no evidence of progression or need for steroids treatment or anticonvulsants for at least 2 weeks prior to randomization.
4. Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event (e.g., intestinal ischemia).

5. Uncontrolled or significant cardiovascular disease:

   • QTcF interval >470 milliseconds (ms).
   • Diagnosed or suspected long QT syndrome.
   • History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
   • Participant has clinically relevant bradycardia of less than 50 beats per minute (bpm), unless the participant has a pacemaker.
   • History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
   • Myocardial infarction within 6 months prior to screening.
   • Uncontrolled angina pectoris within 6 months prior to screening.
   • New York Heart Association (NYHA) Class 3 or 4 congestive heart failure (CHF).
   • Left ventricular ejection fraction \<50% or institutional lower limit of normal as measured by echocardiography or multigated acquisition scan (MUGA) scan.
   • Coronary/peripheral artery bypass graft within 6 months prior to screening.
   • Prior history of hypertensive crisis (common terminology criteria for adverse events [CTCAE] Grade 4) or hypertensive encephalopathy or uncontrolled hypertension CTCAE Grade greater than equal to (≥)3 hypertension as per National Cancer Institute (NCI) CTCAE version 6.0.
   • Complete left or right bundle branch block.
6. Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE), and any radiographic features consistent with ILA, including but not limited to extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing.
7. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the trial enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.

8. Chronic steroid treatment (>10 mg/day prednisone [or equivalent] per day), with the exception of the following:

   • Inhaled steroids for asthma or chronic obstructive pulmonary disease (COPD).
   • Mineralocorticoids (e.g., fludrocortisone) for participants with orthostatic hypotension.
   • Topical steroids for mild skin conditions.
   • Low-dose supplemental corticosteroids for adrenocortical insufficiency.
   • Premedication for treatment groups and/or premedication in case of any hypersensitivity.
   • Intra-articular steroid injections.
9. History of malignancy other than epithelial OVC, primary peritoneal cancer, or fallopian tube cancer within 3 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, ductal carcinoma in situ, or Stage 1 uterine cancer).
10. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE version 6.0, Grade ≤1 or baseline.
11. Has current, clinically relevant bowel obstruction (including subocclusive disease) including obstruction related to underlying epithelial OVC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess.
12. History of severe hypersensitivity (≥ Grade 3) or any known contraindication to R-DXd or any excipients in R-DXd.
13. Has active or uncontrolled Human Immunodeficiency Virus (HIV) infection.
14. Has any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses or active infection, substance abuse) or other factors that, in the investigator's opinion, makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required;
15. Has active or uncontrolled HBV infection. Hepatitis B screening testing is required.
16. Has active or uncontrolled hepatitis C virus (HCV) infection. Hepatitis C screening testing is required.
17. Female who is pregnant or breastfeeding or intends to become pregnant during the trial.
18. Psychological, social, familial, or geographical factors that would prevent regular follow-up (FU).
19. Has a history of receiving live-attenuated vaccine (messenger ribonucleic acid [mRNA] and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to trial intervention.

20. Participants are ineligible if they have a history of any contraindication included in the approved local label for the control group treatment.

    Additional Exclusion Criteria for Bevacizumab Participants:

21. Has a history of arterial thromboembolic events, hemorrhage, hemoptysis, active gastrointestinal bleeding that occurred within 6 months before randomization.
22. Participants with history of serious, non-healing wound, active ulcer or untreated bone fracture.
23. History of vascular endothelial growth factor (VEGF) therapy related abdominal fistula or gastrointestinal perforation.
24. Participants who discontinued bevacizumab during the second (last) platinum-based chemotherapy due to any AE related to bevacizumab are not eligible to receive bevacizumab.
25. Severe hypersensitivity (≥Grade 3) to bevacizumab and/or any of its excipients. Participants with known sensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies are prohibited from receiving bevacizumab during the trial.
26. Participants who have had a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury (e.g., long-bone fracture requiring surgery) as per investigator judgment within 28 days prior to the first date of treatment on this trial, or anticipation of need for major surgical procedure during the course of the trial; participants with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment in the trial.