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NCT06843447PHASE1, PHASE2Recruiting

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

Merck Sharp & Dohme LLC

Start Date

4/15/2025

Completion Date

3/27/2029

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

BIOLOGICAL

Raludotatug Deruxtecan

DRUG

Carboplatin

DRUG

Paclitaxel

BIOLOGICAL

Bevacizumab

DRUG

Rescue Medication

BIOLOGICAL

Pembrolizumab

DRUG

Gemcitabine

DRUG

Pegylated liposomal doxorubicin

Interested in This Trial?

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Conditions

Ovarian Cancer Recurrent

Locations

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

New Haven, Connecticut 06510

United States

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

Louisville, Kentucky 40202

United States

Dana-Farber Cancer Institute ( Site 0015)

Boston, Massachusetts 02215

United States

Memorial Sloan Kettering Cancer Center ( Site 0003)

New York, New York 10065

United States

OU Health University of Oklahoma Medical Center ( Site 7000)

Oklahoma City, Oklahoma 73104

United States

Texas Oncology - DFW ( Site 8000)

Fort Worth, Texas 76104

United States

Houston Methodist Hospital ( Site 0010)

Houston, Texas 77030

United States

START Mountain Region ( Site 0008)

West Valley City, Utah 84119

United States

University of Virginia Health System ( Site 0011)

Charlottesville, Virginia 22908

United States

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

Montreal, Quebec H2X 0A9

Canada

McGill University Health Centre ( Site 0100)

Montreal, Quebec H4A 3J1

Canada

Rambam Health Care Campus ( Site 0202)

Haifa, 3109601

Israel

Shaare Zedek Medical Center ( Site 0201)

Jerusalem, 9103102

Israel

Rabin Medical Center ( Site 0203)

Petah Tikva, 4941492

Israel

Sheba Medical Center ( Site 0200)

Ramat Gan, 5265601

Israel

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

L'Hospitalet de Llobregat, Barcelona 08908

Spain

HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA ( Site 0307)

Majadhonda, Madrid 28222

Spain

Clinica Universidad de Navarra ( Site 0301)

Madrid, Madrid, Comunidad de 28027

Spain

Hospital General Universitario de Valencia ( Site 0305)

Valencia, Valenciana, Comunitat 46014

Spain

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

Barcelona, 08035

Spain

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

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre ( Site 0304)

Madrid, 28041

Spain

Hospital Universitario Virgen de la Victoria ( Site 0306)

Málaga, 29010

Spain

University Hospitals Sussex NHS Foundation Trust ( Site 0404)

Brighton, East Sussex BN2 1ES

United Kingdom

Royal Marsden Hospital ( Site 0402)

Fulham, England SW3 6JJ

United Kingdom

The Royal Marsden NHS Foundation Trust. ( Site 0403)

Sutton, England SM2 5PT

United Kingdom

Barts Health NHS Trust ( Site 0401)

London, London, City of E1 1RD

United Kingdom

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

London, London, City of SE1 3SS

United Kingdom

The Christie NHS Foundation Trust ( Site 0405)

Manchester, M20 4BX

United Kingdom