A Clinical Trial of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab in Participants With Ovarian Cancer Who Have Progressed During Treatment With PARP-inhibitors Treatment on First Line Maintenance (MK-5909-008/ENGOT-ov107/GOG-3142 / REJOICE-Ovarian05)

Phase 3Not Yet RecruitingNCT07743164

Merck Sharp & Dohme LLC646 enrolled

Overview

Researchers are looking for new ways to treat advanced, high-grade ovarian cancer (OC). Advanced means the cancer has spread to other parts of the body (metastatic) and may not be removed with surgery. High-grade means the cancer cells grow and spread quickly. This trial includes types of OC that started in cells that cover the ovaries, in the lining of the belly, or in the fallopian tubes. The usual treatment for high-grade OC may include one or both of these: * Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing. * Bevacizumab, which is a targeted therapy that works to control how specific types of cancer cells grow and spread and targets tumor blood vessels. Researchers want to learn about the trial medicine, raludotatug deruxtecan (also called R-DXd or MK-5909), when given with and without bevacizumab and how participants respond to it. R-DXd is an antibody drug conjugate (ADC). An ADC is a type of medicine that attaches to a specific target on cancer cells and delivers treatment to destroy those cells. The goals of this trial are to learn if participants who receive R-DXd, with or without bevacizumab, live longer overall and without their cancer growing or spreading compared to those who receive usual treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

646

Conditions

Ovarian Cancer Peritoneal Cancer

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

The main inclusion criteria include but are not limited to the following: * Has a histologically or cytologically documented advanced high-grade serous or high-grade endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer. * Has received 1 line of platinum-based therapy with a minimum of 4 cycles of platinum-doublet chemotherapy and have platinum-sensitive disease. * Has received a poly (ADP-ribose) polymerase inhibitor (PARPi) as maintenance treatment after the first line platinum-based chemotherapy course and experienced radiographic progression during treatment or within 42 days of the last dose of PARPi. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization. * Has recovered from any AEs due to previous anticancer therapies. The main exclusion criteria include but are not limited to the following: * Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer. * Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active GI bleeding within 6 months before randomization. * Has uncontrolled or significant cardiovascular disease. * Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of randomization, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), or prior pneumonectomy. * Has received chronic steroid treatment, with some exceptions. * Has current, clinically relevant bowel obstruction (including subocclusive disease) including obstruction related to underlying epithelial ovarian cancer, abdominal fistula or GI perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam. * Has known additional malignancy that is progressing or has required active treatment within the past 3 years.

Outcomes

Primary Outcomes

Progression-free Survival (PFS)

PFS is defined as the time from randomization to the first documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. Disease progression 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 demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered disease progression. PFS as assessed by blinded independent central review (BICR) will be presented.

Time frame: Up to approximately 3 years

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 4 years

Secondary Outcomes

Number of Participants who Experience One or More Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Time frame: Up to approximately 3 years

Number of Participants who Discontinue Study Intervention Due to an AE

Time frame: Up to approximately 3 years

Objective Response Rate (ORR)

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

Time frame: Up to approximately 3 years

Duration of Response (DOR)

For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. Per RECIST 1.1, disease progression (DP) is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered DP.

Time frame: Up to approximately 3 years

Progression-free Survival 2 (PFS2)

PFS2 is defined as the time from randomization to the documented subsequent objective disease progression after initiation of new anticancer therapy or death due to any cause, whichever occurs first.

Time frame: Up to approximately 4 years

Time to First Subsequent Anticancer Treatment (TFST)

TFST is defined as the time from randomization to initiation of first subsequent anticancer treatment or death due to any cause, whichever occurs first.

Time frame: Up to approximately 3 years

Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire 30- (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

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 Items 29 and 30 combined score will be presented.

Time frame: Baseline and at designated time points up to approximately 3 years

Change from Baseline in EORTC Quality of Life Questionnaire Ovarian Cancer Module 28 (QLQ-OV28) Abdominal/Gastrointestinal (GI) Scale

EORTC QLQ-OV28 is an ovarian cancer-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.

Time frame: Baseline and at designated time points up to approximately 3 years

A Clinical Trial of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab in Participants With Ovarian Cancer Who Have Progressed During Treatment With PARP-inhibitors Treatment on First Line Maintenance (MK-5909-008/ENGOT-ov107/GOG-3142 / REJOICE-Ovarian05)

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts