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RecruitingInterventionalPhase 1/Phase 2

A Phase 1b/2 Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan With or Without Other Anticancer Investigational Agents in Participants With High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Relapsed After Prior Platinum-based Chemotherapy

NCT ID: NCT06843447Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-12

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 other treatments and if people tolerate them together. They also want to learn how many people have the cancer respond (gets smaller or goes away) to the treatments.

Detailed description

This study has 2 parts: Part 1 is a dose escalation phase of R-DXd. Part 2 is the expansion phase and will use the Recommended Phase 2 Dose (RP2D) of R-DXd determined in Part 1.

Arms & interventions

  • BiologicalRaludotatug Deruxtecan

    IV infusion on Day 1 of every 3-week cycle.

  • DrugCarboplatin

    IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.

  • DrugPaclitaxel

    IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.

  • BiologicalBevacizumab

    IV infusion on Day 1 of every 3-week cycle.

  • DrugRescue Medication

    Includes 5-HT3 Serotonin Receptor Antagonist, NK-1 receptor antagonist, and corticosteroid, administered per protocol.

  • BiologicalPembrolizumab

    IV infusion on Day 1 of every 3-week cycle for a maximum of 35 cycles.

  • DrugGemcitabine

    IV injection on days 1 and 8 of each 3-week Cycle

  • DrugPegylated liposomal doxorubicin

    IV injection administered on Day 1 of each 4-week cycle

Outcome measures

Primary

  • Part 1: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)

    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.

    Time frame: Up to 21 days

  • Part 1: Number of Participants with 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. The number of participants with one or more AEs will be reported.

    Time frame: Up to approximately 3 years

  • Part 1: Number of Participants who Discontinue Study Intervention Due to an AE

    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.

    Time frame: Up to approximately 3 years

  • Part 2: 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

Secondary

  • Part 1: Objective Response Rate (ORR)

    Time frame: Up to approximately 3 years

  • Part 2: Duration of Response (DOR)

    Time frame: Up to approximately 3 years

  • Part 2: Progression-free Survival (PFS)

    Time frame: Up to approximately 3 years

  • Part 2: Overall Survival (OS)

    Time frame: Up to approximately 3 years

  • Part 2: Number of Participants with One or More AEs

    Time frame: Up to approximately 3 years

  • Part 2: Number of Participants who Discontinue Study Intervention Due to an AE

    Time frame: Up to approximately 3 years

Eligibility criteria

Sex: FemaleAge: 18 Years and olderHealthy volunteers: No
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 Arms 2 and 3: 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 and Cohort B-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-resistant disease). Participants must have received no more than 1 prior bevacizumab-containing systemic treatment regimen * Participants in Cohort B-1 and Cohort B-2: 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/randomization * 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/randomization * Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening * Participants in Cohort C-1 and Cohort D: Has relapsed disease after 1 prior line of therapy, radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease) and progressed during prior treatment with PARPi in the first-line setting * Cohort A-2 Arms 1, 2, and 3: Has relapsed disease after 1 prior line of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease) Exclusion Criteria: * Has any of the following within 6 months before allocation/randomization: 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 any history of interstitial lung disease (ILD)/pneumonitis irrespective of prior steroid use, current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening * Has active infection requiring systemic therapy * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Study locations (8)

Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0019)

New Haven, Connecticut, 06510

Recruiting
Study Coordinator · Contact

The University of Louisville, James Graham Brown Cancer Center ( Site 0009)

Louisville, Kentucky, 40202

Recruiting
Study Coordinator · Contact

Dana-Farber Cancer Institute ( Site 0015)

Boston, Massachusetts, 02215

Recruiting
Study Coordinator · Contact

Memorial Sloan Kettering Cancer Center ( Site 0003)

New York, New York, 10065

Recruiting
Study Coordinator · Contact

OU Health University of Oklahoma Medical Center ( Site 7000)

Oklahoma City, Oklahoma, 73104

Recruiting
Study Coordinator · Contact

Houston Methodist Hospital ( Site 0010)

Houston, Texas, 77030

Recruiting
Study Coordinator · Contact

START Mountain Region ( Site 0008)

West Valley City, Utah, 84119

Recruiting
Study Coordinator · Contact

University of Virginia Health System ( Site 0011)

Charlottesville, Virginia, 22908

Recruiting
Study Coordinator · Contact
A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003) | Cancerify