A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003)

Phase 1

Recruiting

• Conditions: Ovarian Cancer Recurrent
• Interventions: Biological: Raludotatug Deruxtecan; Drug: Carboplatin; Drug: Paclitaxel; Biological: Bevacizumab

• Registration Number: NCT06843447
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Researchers are looking for other ways to treat relapsed high-grade serous ovarian cancer. Relapsed means the cancer came back after treatment. High-grade means the cancer cells grow and spread quickly. Serous means the cancer started in the cells that cover the ovaries, the lining of the belly, or in the fallopian tubes.

Standard treatment (usual treatment) for people with relapsed high-grade serous ovarian cancer may include:

* Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing

* Targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread

Raludotatug deruxtecan (R-DXd) is a study treatment that is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to know if R-DXd is safe to take with standard treatment and if people tolerate them together.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-20
• Study First Submitted QC: 2025-02-20
• Study First Posted: 2025-02-25
• Status Verified: 2025-04
• Study Start: 2025-04-15
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27
• Primary Completion: 2029-03-27
• Study Completion: 2029-03-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 78

Inclusion Criteria

• Has pathologically documented diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
• Has measurable disease per Response Evaluation Criteria In Solid Tumors 1.1
• Participants in Cohort A-1 Arm 1 and Arm 2: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease).
• Participants in Cohort B-1: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression <6 months (<180 days) after the last dose of platinum-based therapy (ie, platinum-resistant disease).
• Participants in Cohort B-1: Is a candidate for bevacizumab treatment
• Has provided tumor tissue from a core or excisional biopsy of a tumor lesion not previously irradiated
• Has an Eastern Cooperative Oncology Group performance status of 0 to 1 assessed within 7 days before allocation
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy
• Participants who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation
• Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

Exclusion Criteria

• Has any of the following within 6 months before allocation: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event
• 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, and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement, or prior pneumonectomy
• Has ≥Grade 2 peripheral neuropathy
• Has received prior treatment with cadherin-6-targeted agents
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before allocation
• Has received prior radiotherapy within 2 weeks of the start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Receives chronic steroid treatment
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active CNS metastases and/or carcinomatous meningitis
• Has history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
• Has active infection requiring systemic therapy
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A-1 Arm 1 (R-DXd + Carboplatin)	Carboplatin	Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan in combination with carboplatin. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.
Cohort A-1 Arm 2 (R-DXd + Paclitaxel)	Raludotatug Deruxtecan	Participants receive escalating doses of IV raludotatug deruxtecan in combination with paclitaxel. Participants can receive up to a maximum of six 3-week cycles of paclitaxel (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.
Cohort A-1 Arm 2 (R-DXd + Paclitaxel)	Paclitaxel	Participants receive escalating doses of IV raludotatug deruxtecan in combination with paclitaxel. Participants can receive up to a maximum of six 3-week cycles of paclitaxel (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.
Cohort B-1 (R-DXd + Bevacizumab)	Bevacizumab	Participants receive escalating doses of IV raludotatug deruxtecan in combination with bevacizumab until disease progression or discontinuation.
Cohort A-1 Arm 1 (R-DXd + Carboplatin)	Raludotatug Deruxtecan	Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan in combination with carboplatin. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.
Cohort B-1 (R-DXd + Bevacizumab)	Raludotatug Deruxtecan	Participants receive escalating doses of IV raludotatug deruxtecan in combination with bevacizumab until disease progression or discontinuation.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)	Up to 21 days	DLTs are defined as toxicities during the DLT evaluation period that are assessed by the investigator to be possibly, probably, or definitely related to study treatment and include: Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia lasting ≥7 days; Grade 3 or higher thrombocytopenia associated with clinically significant bleeding; Grade 4 lymphocytopenia lasting ≥14 days; Grade 4 anemia of any duration; any other Grade 4 hematologic toxicity lasting ≥7 days; febrile neutropenia Grade 3 or Grade 4 meeting pre-specifications; pre-specified hepatic organ toxicities; all Grade 3 or higher other nonhematologic toxicities except those pre-specified; other pre-specified nonhematologic toxicities; any delay in treatment with the planned dose of ≥21 days or discontinuation of treatment due to a toxicity during the DLT evaluation period, or Grade 5 toxicity. The number of participants with DLTs will be reported.
Number of Participants with One or More Adverse Events (AEs)	Up to approximately 3 years	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. The number of participants with one or more AEs will be reported.
Number of Participants who Discontinue Study Intervention Due to an AE	Up to approximately 3 years	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. The number of participants who discontinue study intervention due to an AE will be reported.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 3 years	ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST 1.1). ORR will be assessed by blinded independent central review (BICR).

Trial Locations

Locations (4)

Rambam Health Care Campus ( Site 0202); 🇮🇱 Haifa, Israel

Shaare Zedek Medical Center ( Site 0201); 🇮🇱 Jerusalem, Israel

Sheba Medical Center ( Site 0200); 🇮🇱 Ramat Gan, Israel

START Mountain Region ( Site 0008); 🇺🇸 West Valley City, Utah, United States