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

NCT06843447 · Merck Sharp & Dohme LLC
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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
About this study
This study has 2 parts: Part 1 is a dose escalation phase of R-DXd. Part 2 is the efficacy expansion phase and will use the Recommended Phase 2 Dose (RP2D) of R-DXd determined in Part 1.
Eligibility criteria
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 2 and Arm 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 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 * 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 * 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 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
Enrollment target: 280 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-04-15
Estimated completion: 2029-03-27
Last updated: 2026-03-27
Interventions
Biological: Raludotatug DeruxtecanDrug: CarboplatinDrug: PaclitaxelBiological: BevacizumabDrug: Rescue MedicationBiological: Pembrolizumab
Primary outcomes
  • 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) (Up to 21 days)
  • Part 1: Number of Participants with One or More Adverse Events (AEs) (Up to approximately 3 years)
  • Part 1: Number of Participants who Discontinue Study Intervention Due to an AE (Up to approximately 3 years)
Sponsor
Merck Sharp & Dohme LLC · industry
With: Daiichi Sankyo
Contacts & investigators
ContactToll Free Number · contact · Trialsites@msd.com · 1-888-577-8839
InvestigatorMedical Director · study_director, Merck Sharp & Dohme LLC
All locations (16)
The University of Louisville, James Graham Brown Cancer Center ( Site 0009)Recruiting
Louisville, Kentucky, United States
Memorial Sloan Kettering Cancer Center ( Site 0003)Recruiting
New York, New York, United States
Houston Methodist Hospital ( Site 0010)Recruiting
Houston, Texas, United States
START Mountain Region ( Site 0008)Recruiting
West Valley City, Utah, United States
University of Virginia Health System ( Site 0011)Recruiting
Charlottesville, Virginia, United States
Rambam Health Care Campus ( Site 0202)Recruiting
Haifa, Israel
Shaare Zedek Medical Center ( Site 0201)Recruiting
Jerusalem, Israel
Sheba Medical Center ( Site 0200)Recruiting
Ramat Gan, Israel
Institut Català d'Oncologia - L'Hospitalet ( Site 0302)Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain
Clinica Universidad de Navarra ( Site 0301)Recruiting
Madrid, Madrid, Comunidad de, Spain
Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0300)Recruiting
Barcelona, Spain
Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0303)Recruiting
Madrid, Spain
Hospital Universitario 12 de Octubre ( Site 0304)Recruiting
Madrid, Spain
Royal Marsden Hospital ( Site 0402)Recruiting
Fulham, England, United Kingdom
The Royal Marsden NHS Foundation Trust. ( Site 0403)Recruiting
Sutton, England, United Kingdom
Barts Health NHS Trust ( Site 0401)Recruiting
London, London, City of, United Kingdom