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

NCT06843447 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 5909-003MK-5909-0032024-514674-47-00U1111-1308-2821REJOICE-Ovarian02
• Study Type: interventional
• Target: 460
• Locations: 5 countries
• Sites: 29

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 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.

Conditions

Ovarian Cancer Recurrent

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Up to approximately 3 years

Secondary Outcomes (6)

• Part 1: Objective Response Rate (ORR)

  Up to approximately 3 years

• Part 2: Duration of Response (DOR)

  Up to approximately 3 years

• Part 2: Progression-free Survival (PFS)

  Up to approximately 3 years

• Part 2: Overall Survival (OS)

  Up to approximately 3 years

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

  Up to approximately 3 years

Study Arms (10)

Cohort A-1 Arm 1 (R-DXd + Carboplatin Dose 1)

EXPERIMENTAL

Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan (R-DXd) in combination with carboplatin at Dose 1. 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.

Biological: Raludotatug Deruxtecan; Drug: Carboplatin; Drug: Rescue Medication

Cohort A-1 Arm 2 (R-DXd + Paclitaxel)

EXPERIMENTAL

Participants receive escalating doses of IV R-DXd in combination with paclitaxel. Participants can receive up to a maximum of six 3-week cycles of paclitaxel (approximately 4 months) and will receive R-DXd until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Drug: Paclitaxel; Drug: Rescue Medication

Cohort A-1 Arm 3 (R-DXd + Carboplatin Dose 2)

EXPERIMENTAL

Participants receive escalating doses of intravenous (IV) R-DXd in combination with carboplatin at Dose 2. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive R-DXd until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Drug: Carboplatin; Drug: Rescue Medication

Cohort B-1 (R-DXd + Bevacizumab)

EXPERIMENTAL

Participants receive escalating doses of IV R-DXd in combination with bevacizumab until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Biological: Bevacizumab; Drug: Rescue Medication

Cohort B-2 (R-DXd RP2D + Bevacizumab)

EXPERIMENTAL

Participants with platinum-resistant recurrent ovarian cancer (PRROC) receive recommended Phase 2 dose (RP2D) of IV R-DXd in combination with bevacizumab until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Biological: Bevacizumab; Drug: Rescue Medication

Cohort C-1 (R-DXd + Pembrolizumab)

EXPERIMENTAL

Participants receive escalating doses of IV R-DXd in combination with pembrolizumab. Participants can receive up to a maximum of thirty-five 3-week cycles of pembrolizumab (approximately 2 years) and will receive R-DXd until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Drug: Rescue Medication; Biological: Pembrolizumab

Cohort D (R-DXd RP2D +/- Bevacizumab)

EXPERIMENTAL

Participants with platinum-sensitive recurrent ovarian cancer (PSROC) receive RP2D of IV R-DXd in combination with or without bevacizumab until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Biological: Bevacizumab; Drug: Rescue Medication

Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab)

EXPERIMENTAL

Participants with PSROC will receive the RP2D of R-DXd in combination with a maximum of 6 cycles of carboplatin with or without bevacizumab, until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Drug: Carboplatin; Biological: Bevacizumab; Drug: Rescue Medication

Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab)

EXPERIMENTAL

Participants with PSROC will receive the RP2D of R-DXd in combination with a maximum of 6 cycles of paclitaxel with or without bevacizumab, until disease progression or discontinuation.

Biological: Raludotatug Deruxtecan; Drug: Paclitaxel; Biological: Bevacizumab; Drug: Rescue Medication

Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)

ACTIVE COMPARATOR

Participants with PSROC will receive one of 3 regimens of investigator's choice of platinum-based doublet chemotherapy with or without bevacizumab. Platinum-based doublet chemotherapy will be administered for maximum of 8 cycles. Bevacizumab can be administered until disease progression or discontinuation.

Drug: Carboplatin; Drug: Paclitaxel; Biological: Bevacizumab; Drug: Gemcitabine; Drug: Pegylated liposomal doxorubicin

Interventions

Paclitaxel DRUG

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

Cohort A-1 Arm 2 (R-DXd + Paclitaxel); Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab); Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)

Bevacizumab BIOLOGICAL

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

Also known as: Includes, based on sourcing:, - Avastin®, - Alymsys®, - MVASI®, - Oyavas®, - Zirabev®, - Vegzelma®, - Aybintio®, - Breztri®

Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab); Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab); Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab); Cohort B-1 (R-DXd + Bevacizumab); Cohort B-2 (R-DXd RP2D + Bevacizumab); Cohort D (R-DXd RP2D +/- Bevacizumab)

Carboplatin DRUG

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

Cohort A-1 Arm 1 (R-DXd + Carboplatin Dose 1); Cohort A-1 Arm 3 (R-DXd + Carboplatin Dose 2); Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab); Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)

Pembrolizumab BIOLOGICAL

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

Cohort C-1 (R-DXd + Pembrolizumab)

Raludotatug Deruxtecan BIOLOGICAL

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

Also known as: MK-5909, R-DXd

Cohort A-1 Arm 1 (R-DXd + Carboplatin Dose 1); Cohort A-1 Arm 2 (R-DXd + Paclitaxel); Cohort A-1 Arm 3 (R-DXd + Carboplatin Dose 2); Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab); Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab); Cohort B-1 (R-DXd + Bevacizumab); Cohort B-2 (R-DXd RP2D + Bevacizumab); Cohort C-1 (R-DXd + Pembrolizumab); Cohort D (R-DXd RP2D +/- Bevacizumab)

Gemcitabine DRUG

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

Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)

Pegylated liposomal doxorubicin DRUG

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

Also known as: PLD

Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)

Rescue Medication DRUG

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

Cohort A-1 Arm 1 (R-DXd + Carboplatin Dose 1); Cohort A-1 Arm 2 (R-DXd + Paclitaxel); Cohort A-1 Arm 3 (R-DXd + Carboplatin Dose 2); Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab); Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab); Cohort B-1 (R-DXd + Bevacizumab); Cohort B-2 (R-DXd RP2D + Bevacizumab); Cohort C-1 (R-DXd + Pembrolizumab); Cohort D (R-DXd RP2D +/- Bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Daiichi Sankyo: collaborator

Study Sites (29)

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

New Haven, Connecticut, 06510, United States

RECRUITING

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

Louisville, Kentucky, 40202, United States

RECRUITING

Dana-Farber Cancer Institute ( Site 0015)

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center ( Site 0003)

New York, New York, 10065, United States

RECRUITING

OU Health University of Oklahoma Medical Center ( Site 7000)

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Texas Oncology - DFW ( Site 8000)

Fort Worth, Texas, 76104, United States

RECRUITING

Houston Methodist Hospital ( Site 0010)

Houston, Texas, 77030, United States

COMPLETED

START Mountain Region ( Site 0008)

West Valley City, Utah, 84119, United States

RECRUITING

University of Virginia Health System ( Site 0011)

Charlottesville, Virginia, 22908, United States

RECRUITING

Centre Hospitalier de l'Université de Montréal ( Site 0102)

Montreal, Quebec, H2X 0A9, Canada

RECRUITING

McGill University Health Centre ( Site 0100)

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Rambam Health Care Campus ( Site 0202)

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center ( Site 0201)

Jerusalem, 9103102, Israel

RECRUITING

Rabin Medical Center ( Site 0203)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 0200)

Ramat Gan, 5265601, Israel

RECRUITING

Institut Català d'Oncologia - L'Hospitalet ( Site 0302)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA ( Site 0307)

Majadhonda, Madrid, 28222, Spain

RECRUITING

Clinica Universidad de Navarra ( Site 0301)

Madrid, Madrid, Comunidad de, 28027, Spain

RECRUITING

Hospital General Universitario de Valencia ( Site 0305)

Valencia, Valenciana, Comunitat, 46014, Spain

RECRUITING

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0300)

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0303)

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre ( Site 0304)

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria ( Site 0306)

Málaga, 29010, Spain

RECRUITING

University Hospitals Sussex NHS Foundation Trust ( Site 0404)

Brighton, East Sussex, BN2 1ES, United Kingdom

RECRUITING

Royal Marsden Hospital ( Site 0402)

Fulham, England, SW3 6JJ, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust. ( Site 0403)

Sutton, England, SM2 5PT, United Kingdom

RECRUITING

Barts Health NHS Trust ( Site 0401)

London, London, City of, E1 1RD, United Kingdom

RECRUITING

Guy s & St Thomas NHS Foundation Trust ( Site 0400)

London, London, City of, SE1 3SS, United Kingdom

RECRUITING

The Christie NHS Foundation Trust ( Site 0405)

Manchester, M20 4BX, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

Carboplatin; Paclitaxel; Bevacizumab; pembrolizumab; Gemcitabine; liposomal doxorubicin; 1-dodecylpyridoxal

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study; therefore, the Sponsor, investigator, and participant will know the intervention administered. Imaging data will be centrally reviewed by independent radiologist(s) without knowledge of participant dose assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: February 25, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): March 27, 2029
• Study Completion (Estimated): March 27, 2029
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (6); US (9); IL (4); ES (8); CA (2)