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

NCT06843447
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
460
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Lead sponsor
Merck Sharp & Dohme LLC
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Start date
2025-04-15
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Number of sites
30
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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.
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Short title
A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003)
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Official title
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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2029-03-27
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First posted
2025-02-25
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Registry last updated
2026-08-14
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Primary completion date
2029-03-27
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Start date
2025-04-15
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Participants
460
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Participant count basis
Estimated
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Planned participants
460
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Protocol amendments
2
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Number of sites
30
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Merck Sharp & Dohme LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06843447
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ClinicalTrials.gov ID
NCT06843447
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Masking description
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.
Sources for study design
clinicaltrials.gov

  1. 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)

    Timeframe: 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.

  2. Part 1: Number of Participants with One or More Adverse Events (AEs)

    Timeframe: 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.

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

    Timeframe: 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.

  4. Part 2: Objective Response Rate (ORR)

    Timeframe: Up to approximately 3 years

    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.

  1. Part 1: Objective Response Rate (ORR)

    Timeframe: 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).

  2. Part 2: Duration of Response (DOR)

    Timeframe: Up to approximately 3 years

    For participants who demonstrate a confirmed 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), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD 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 PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.

  3. Part 2: Progression-free Survival (PFS)

    Timeframe: Up to approximately 3 years

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

  4. Part 2: Overall Survival (OS)

    Timeframe: Up to approximately 3 years

    OS is defined as the time from the first dose of study treatment to death due to any cause.

  5. Part 2: Number of Participants with One or More AEs

    Timeframe: 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.

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

    Timeframe: 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.

Sources for outcomes
clinicaltrials.gov

Sex
Female
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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)

  • 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
Sources for eligibility
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  • Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0019)New Haven, United StatesRecruiting
  • The University of Louisville, James Graham Brown Cancer Center ( Site 0009)Louisville, United StatesRecruiting
  • TRIALS 365 ( Site 0020)Shreveport, United StatesRecruiting
  • Dana-Farber Cancer Institute ( Site 0015)Boston, United StatesRecruiting
  • Memorial Sloan Kettering Cancer Center ( Site 0003)New York, United StatesRecruiting
  • OU Health University of Oklahoma Medical Center ( Site 7000)Oklahoma City, United StatesRecruiting
  • Texas Oncology - DFW ( Site 8000)Fort Worth, United StatesRecruiting
  • Houston Methodist Hospital ( Site 0010)Houston, United StatesCompleted
  • START Mountain Region ( Site 0008)West Valley City, United StatesRecruiting
  • University of Virginia Health System ( Site 0011)Charlottesville, United StatesRecruiting
  • Centre Hospitalier de l'Université de Montréal ( Site 0102)Montreal, CanadaRecruiting
  • McGill University Health Centre ( Site 0100)Montreal, CanadaRecruiting
  • Rambam Health Care Campus ( Site 0202)Haifa, IsraelRecruiting
  • Shaare Zedek Medical Center ( Site 0201)Jerusalem, IsraelRecruiting
  • Rabin Medical Center ( Site 0203)Petah Tikva, IsraelRecruiting
  • Sheba Medical Center ( Site 0200)Ramat Gan, IsraelRecruiting
  • Institut Català d'Oncologia - L'Hospitalet ( Site 0302)L'Hospitalet de Llobregat, SpainRecruiting
  • HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA ( Site 0307)Majadhonda, SpainRecruiting
  • Clinica Universidad de Navarra ( Site 0301)Madrid, SpainRecruiting
  • Hospital General Universitario de Valencia ( Site 0305)Valencia, SpainRecruiting
  • Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0300)Barcelona, SpainRecruiting
  • Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0303)Madrid, SpainRecruiting
  • Hospital Universitario 12 de Octubre ( Site 0304)Madrid, SpainRecruiting
  • Hospital Universitario Virgen de la Victoria ( Site 0306)Málaga, SpainRecruiting
  • University Hospitals Sussex NHS Foundation Trust ( Site 0404)Brighton, United KingdomRecruiting

And 5 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • MK-5909-003
  • U1111-1308-2821
  • 2024-514674-47-00
Sources for references
clinicaltrials.gov

Related records

Drugs (8)

Collaborators (1)

Lead sponsors (1)

Conditions (1)

Targets (33)