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)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 646
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Standard of Care
Participants receive 6 to 8 cycles of investigator's choice of one of three options of platinum-based chemotherapy with or without IV bevacizumab. Bevacizumab treatment if elected, will continue until PD, unacceptable toxicity, or other protocol specified reason for discontinuation
干预措施: Gemcitabine (Drug)
Standard of Care
Participants receive 6 to 8 cycles of investigator's choice of one of three options of platinum-based chemotherapy with or without IV bevacizumab. Bevacizumab treatment if elected, will continue until PD, unacceptable toxicity, or other protocol specified reason for discontinuation
干预措施: Carboplatin (Drug)
R-DXd +/- Bevacizumab
Participants will receive intravenous (IV) raludotatug deruxtecan (R-DXd) with or without IV bevacizumab for up to 2 years until progressive disease (PD), unacceptable toxicity, or other protocol-specified reason for discontinuation
干预措施: R-DXd (Biological)
R-DXd +/- Bevacizumab
Participants will receive intravenous (IV) raludotatug deruxtecan (R-DXd) with or without IV bevacizumab for up to 2 years until progressive disease (PD), unacceptable toxicity, or other protocol-specified reason for discontinuation
干预措施: Bevacizumab (Drug)
Standard of Care
Participants receive 6 to 8 cycles of investigator's choice of one of three options of platinum-based chemotherapy with or without IV bevacizumab. Bevacizumab treatment if elected, will continue until PD, unacceptable toxicity, or other protocol specified reason for discontinuation
干预措施: Bevacizumab (Drug)
Standard of Care
Participants receive 6 to 8 cycles of investigator's choice of one of three options of platinum-based chemotherapy with or without IV bevacizumab. Bevacizumab treatment if elected, will continue until PD, unacceptable toxicity, or other protocol specified reason for discontinuation
干预措施: Paclitaxel (Drug)
Standard of Care
Participants receive 6 to 8 cycles of investigator's choice of one of three options of platinum-based chemotherapy with or without IV bevacizumab. Bevacizumab treatment if elected, will continue until PD, unacceptable toxicity, or other protocol specified reason for discontinuation
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to approximately 24 months
PFS is defined as the time from randomization to the first documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered disease progression. PFS as assessed by blinded independent central review (BICR) will be presented.
Overall Survival (OS)
时间窗: Up to approximately 24 months
OS is defined as the time from randomization to death due to any cause.
Progression-free Survival (PFS)
时间窗: Up to approximately 3 years
PFS is defined as the time from randomization to the first documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered disease progression. PFS as assessed by blinded independent central review (BICR) will be presented.
Overall Survival (OS)
时间窗: Up to approximately 4 years
OS is defined as the time from randomization to death due to any cause.
次要结局
- Number of Participants who Experience One or More Adverse Events (AEs)(Up to approximately 24 months)
- Number of Participants who Discontinue Study Intervention Due to an AE(Up to approximately 24 months)
- Objective Response Rate (ORR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Progression-free Survival 2 (PFS2)(Up to approximately 24 months)
- Time to First Subsequent Anticancer Treatment (TFST)(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(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(Baseline and at designated time points up to approximately 24 months)
- Number of Participants who Experience One or More Adverse Events (AEs)(Up to approximately 3 years)
- Number of Participants who Discontinue Study Intervention Due to an AE(Up to approximately 3 years)
- Objective Response Rate (ORR)(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)
- Progression-free Survival 2 (PFS2)(Up to approximately 4 years)
- Time to First Subsequent Anticancer Treatment (TFST)(Up to approximately 3 years)
- 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(Baseline and at designated time points up to approximately 3 years)
- Change from Baseline in EORTC Quality of Life Questionnaire Ovarian Cancer Module 28 (QLQ-OV28) Abdominal/Gastrointestinal (GI) Scale(Baseline and at designated time points up to approximately 3 years)