A Clinical Trial of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab in Participants With Ovarian Cancer Who Have Progressed During Treatment With PARP-inhibitors Treatment on First Line Maintenance (MK-5909-008/ENGOT-ov107/GOG-3142 / REJOICE-Ovarian05)

Официальное название

A Phase 3, Open-Label, Multicenter, Randomized Study of Raludotatug Deruxtecan (MK-5909, R-DXd) With or Without Bevacizumab Versus Standard-of-Care Platinum-Based Doublet Chemotherapy With or Without Bevacizumab in Participants With Advanced Platinum-Sensitive High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Progressed During First-Line PARPi Maintenance (ENGOT-ov107 / GOG-3142 / REJOICE-Ovarian05)

Обзор

Researchers are looking for new ways to treat advanced, high-grade ovarian cancer (OC). Advanced means the cancer has spread to other parts of the body (metastatic) and may not be removed with surgery. High-grade means the cancer cells grow and spread quickly. This trial includes types of OC that started in cells that cover the ovaries, in the lining of the belly, or in the fallopian tubes. The usual treatment for high-grade OC may include one or both of these: * Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing. * Bevacizumab, which is a targeted therapy that works to control how specific types of cancer cells grow and spread and targets tumor blood vessels. Researchers want to learn about the trial medicine, raludotatug deruxtecan (also called R-DXd or MK-5909), when given with and without bevacizumab and how participants respond to it. R-DXd is an antibody drug conjugate (ADC). An ADC is a type of medicine that attaches to a specific target on cancer cells and delivers treatment to destroy those cells. The goals of this trial are to learn if participants who receive R-DXd, with or without bevacizumab, live longer overall and without their cancer growing or spreading compared to those who receive usual treatment.

Вмешательства

• Биопрепарат R-DXd
  R-DXd alone or in combination with bevacizumab administered via IV infusion
• Препарат Bevacizumab
  Bevacizumab 10 or 15 mg/kg administered via IV infusion on day 1 q3w
• Препарат Carboplatin
  Carboplatin area under the curve (AUC) 5 mg/mL\*min or AUC 4 mg/mL\*min administered on day 1 q3w for a maximum of 8 cycles
• Препарат Paclitaxel
  Paclitaxel 175 mg/m\^2 administered via IV infusion on day 1 q3w for a maximum of 8 cycles
• Препарат Gemcitabine
  Gemcitabine 1000 mg/mL administered via IV infusion on day 1 and day 8 of each 3-week cycle for a maximum of 8 cycles
• Препарат Pegylated liposomal doxorubicin (PLD)
  PLD 30 mg/m\^2 administered via IV infusion on day 1 of each 4-week cycles for a maximum of 8 cycles

Первичные конечные точки

• Progression-free Survival (PFS) [Срок оценки: Up to approximately 24 months]
• Overall Survival (OS) [Срок оценки: Up to approximately 24 months]

Вторичные конечные точки (8)

• Number of Participants who Experience One or More Adverse Events (AEs) [Срок оценки: Up to approximately 24 months]
• Number of Participants who Discontinue Study Intervention Due to an AE [Срок оценки: Up to approximately 24 months]
• Objective Response Rate (ORR) [Срок оценки: Up to approximately 24 months]
• Duration of Response (DOR) [Срок оценки: Up to approximately 24 months]
• Progression-free Survival 2 (PFS2) [Срок оценки: Up to approximately 24 months]
• Time to First Subsequent Anticancer Treatment (TFST) [Срок оценки: Up to approximately 24 months]
• Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire 30- (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [Срок оценки: Baseline and at designated time points up to approximately 24 months]
• Change from Baseline in EORTC Quality of Life Questionnaire Ovarian Cancer Module 28 (QLQ-OV28) Abdominal/Gastrointestinal (GI) Scale [Срок оценки: Baseline and at designated time points up to approximately 24 months]

Критерии участия

The main inclusion criteria include but are not limited to the following:

• Has a histologically or cytologically documented advanced high-grade serous or high-grade endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
• Has received 1 line of platinum-based therapy with a minimum of 4 cycles of platinum-doublet chemotherapy and have platinum-sensitive disease.
• Has received a poly (ADP-ribose) polymerase inhibitor (PARPi) as maintenance treatment after the first line platinum-based chemotherapy course and experienced radiographic progression during treatment or within 42 days of the last dose of PARPi.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization.
• Has recovered from any AEs due to previous anticancer therapies.

The main exclusion criteria include but are not limited to the following:

• Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer.
• Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active GI bleeding within 6 months before randomization.
• 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 (ie, pulmonary emboli within 3 months of randomization, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), or prior pneumonectomy.
• Has received chronic steroid treatment, with some exceptions.
• Has current, clinically relevant bowel obstruction (including subocclusive disease) including obstruction related to underlying epithelial ovarian cancer, abdominal fistula or GI perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07743164 · 5909-008 · ENGOT-ov107 · GOG-3142 · REJOICE-Ovarian05 (RO-05) · U1111-1333-3042 · MK-5909-008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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