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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (6)

• Part 1: Objective Response Rate (ORR) [Срок оценки: Up to approximately 3 years]
• Part 2: Duration of Response (DOR) [Срок оценки: Up to approximately 3 years]
• Part 2: Progression-free Survival (PFS) [Срок оценки: Up to approximately 3 years]
• Part 2: Overall Survival (OS) [Срок оценки: Up to approximately 3 years]
• Part 2: Number of Participants with One or More AEs [Срок оценки: Up to approximately 3 years]
• Part 2: Number of Participants who Discontinue Study Intervention Due to an AE [Срок оценки: Up to approximately 3 years]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• 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
• … и ещё 1 центр

Испания · 8 центров

• 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

Великобритания · 6 центров

• 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

Израиль · 4 центра

• 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

Канада · 2 центра

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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