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

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

Overview

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.

Interventions

• Biological Raludotatug Deruxtecan
  IV infusion on Day 1 of every 3-week cycle.
• Drug Carboplatin
  IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.
• Drug Paclitaxel
  IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.
• Biological Bevacizumab
  IV infusion on Day 1 of every 3-week cycle.
• Drug Rescue Medication
  Includes 5-HT3 Serotonin Receptor Antagonist, NK-1 receptor antagonist, and corticosteroid, administered per protocol.
• Biological Pembrolizumab
  IV infusion on Day 1 of every 3-week cycle for a maximum of 35 cycles.
• Drug Gemcitabine
  IV injection on days 1 and 8 of each 3-week Cycle
• Drug Pegylated liposomal doxorubicin
  IV injection administered on Day 1 of each 4-week cycle

Primary outcome measures

• 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) [Time frame: Up to 21 days]
• Part 1: Number of Participants with One or More Adverse Events (AEs) [Time frame: Up to approximately 3 years]
• Part 1: Number of Participants who Discontinue Study Intervention Due to an AE [Time frame: Up to approximately 3 years]
• Part 2: Objective Response Rate (ORR) [Time frame: Up to approximately 3 years]

Secondary outcome measures (6)

• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 9 centers

• Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0019) — New Haven
• The University of Louisville, James Graham Brown Cancer Center ( Site 0009) — Louisville
• Dana-Farber Cancer Institute ( Site 0015) — Boston
• Memorial Sloan Kettering Cancer Center ( Site 0003) — New York
• OU Health University of Oklahoma Medical Center ( Site 7000) — Oklahoma City
• Texas Oncology - DFW ( Site 8000) — Fort Worth
• Houston Methodist Hospital ( Site 0010) — Houston
• START Mountain Region ( Site 0008) — West Valley City
• … and 1 more center

Spain · 8 centers

• Institut Català d'Oncologia - L'Hospitalet ( Site 0302) — L'Hospitalet de Llobregat
• HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA ( Site 0307) — Majadhonda
• Clinica Universidad de Navarra ( Site 0301) — Madrid
• Hospital General Universitario de Valencia ( Site 0305) — Valencia
• Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0300) — Barcelona
• Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0303) — Madrid
• Hospital Universitario 12 de Octubre ( Site 0304) — Madrid
• Hospital Universitario Virgen de la Victoria ( Site 0306) — Málaga

United Kingdom · 6 centers

• University Hospitals Sussex NHS Foundation Trust ( Site 0404) — Brighton
• Royal Marsden Hospital ( Site 0402) — Fulham
• The Royal Marsden NHS Foundation Trust. ( Site 0403) — Sutton
• Barts Health NHS Trust ( Site 0401) — London
• Guy s & St Thomas NHS Foundation Trust ( Site 0400) — London
• The Christie NHS Foundation Trust ( Site 0405) — Manchester

Israel · 4 centers

• Rambam Health Care Campus ( Site 0202) — Haifa
• Shaare Zedek Medical Center ( Site 0201) — Jerusalem
• Rabin Medical Center ( Site 0203) — Petah Tikva
• Sheba Medical Center ( Site 0200) — Ramat Gan

Canada · 2 centers

• Centre Hospitalier de l'Université de Montréal ( Site 0102) — Montreal
• McGill University Health Centre ( Site 0100) — Montreal

Identifiers

NCT: NCT06843447 · 5909-003 · MK-5909-003 · 2024-514674-47-00 · U1111-1308-2821 · REJOICE-Ovarian02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗