A Study of Raludotatug Deruxtecan With or Without Bevacizumab as First-Line Maintenance Treatment in Non-HRD-Positive Advanced Ovarian Cancer (MK-5909-006, (ENGOT-ov102/GOG-3141/ REJOICE-Ovarian 04)

• R-DXd (Biological): R-DXd administered as an intravenously (IV) infusion
• Bevacizumab (Drug), also known as Avastin®, MVASI®, Altuzan®: Administered as an intravenously IV infusion

Primary outcomes

• Progression-Free Survival (PFS) [Up to approximately 4 years]: PFS is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by blinded independent central review (BICR) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
• Overall Survival (OS) [Up to approximately 5.5 years]: OS is defined as the time from randomization to death due to any cause.

Secondary outcomes

• Progression-Free Survival 2 (PFS2) [Up to approximately 5.5 years]: PFS2 as assessed by investigator is defined from time from randomization to the documented subsequent objective disease progression after initiation of new anticancer therapy, or death from any cause, whichever occurs first
• Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Score (Item 30) Using the European Organisation for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) [Baseline and up to approximately 4 years]: The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 score will be presented.
• Change From Baseline in Abdominal/Gastrointestinal (GI) Symptoms Combined Score Using the EORTC QLQ-Ovarian Cancer Module 28 (OV28) [Baseline and up to approximately 4 years]: EORTC QLQ-OV28 is an OC-specific module to supplement the EORTC QLQ-C30. Participant responses to the 6 abdominal/GI symptoms scale questions are scored on a 4-point scale (1=not at all, 4=very much). The combined score is computed by averaging the raw scores of the 6 items and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. The change from baseline in abdominal and gastrointestinal symptoms (EORTC QLQ-OC28 Items 31-36) score will be presented. A lower score indicates a better outcome.
• Number of Participants who Experience an Adverse Event (AE) [Up to approximately 4 years]: An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.
• Number of Participants who Discontinue Study Treatment due to an AE [Up to approximately 4 years]: An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a new, histologically confirmed diagnosis of International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV epithelial ovarian cancer (EOC) (high grade serous or high grade endometrioid), fallopian tube cancer, or primary peritoneal cancer
* Has undergone primary debulking surgery (PDS) or interval debulking surgery (IDS)
* Has completed first-line (1L) platinum-based chemotherapy, with a response of stable disease, partial response, complete response or no evidence of disease per protocol
* Has provided tumor tissue that is not previously irradiated
* Who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except alopecia or vitiligo), as assessed by the physician investigator
* Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has non-serous or non-endometrioid high-grade epithelial histology, nonepithelial ovarian cancers, borderline tumors, mucinous tumor, seromucinous tumor that is predominately mucinous, malignant Brenner's tumor, and undifferentiated carcinoma
* Has received 1L platinum-based chemotherapy without bevacizumab and have a response of SD or PR at the time of screening
* Has received prior systemic anticancer therapy, with the exception of the first-line platinum-based chemotherapy required by the inclusion criteria
* Has not recovered from major surgery or has ongoing surgical complications
* Has a homologous recombination deficiency (HRD)-positive, unknown, or inconclusive tumor status as determined by the central laboratory
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder or prior pneumonectomy
* Has current, clinically relevant bowel obstruction including obstruction related to underlying EOC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam
* HIV-infected participants with a history of Kaposi's sarcoma and/or multicentric Castleman disease
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has active infection requiring systemic therapy

NIH grants: 2025