A Randomized, Double-blind, Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Tesaro, Inc.
- 入组人数
- 1,400
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Ovarian cancer is a heterogeneous disease, characterized by complex molecular and genetic changes. The high expression of vascular endothelial growth factor (VEGF) receptor, programmed death receptor ligands 1 (PD-L1) expression, and deoxyribonucleic acid (DNA) damage in ovarian tumors provide several targets for treatment and maintenance of disease response. Given the unmet medical need of participants with advanced or metastatic ovarian cancer, this study design will enable investigators to provide participants with current SOC for ovarian cancer for the duration of the study. This is a global, multicenter, randomized, double-blind, controlled Phase 3 study that will primarily compare the progression-free survival (PFS) for participants receiving dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus participants receiving SOC with chemotherapy followed by niraparib maintenance. This comparison will be investigated in participants of newly diagnosed stage III or IV advanced non-mucinous epithelial ovarian cancer participants and also to compare PFS of all participants with Stage III or IV high-grade non-mucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab (TSR-042), and niraparib to SOC platinum-based combination therapy. The currently recommended SOC therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab. Participants will receive SOC during the chemotherapy Run-In period (cycle 1) before randomization to study treatment (cycle 2). Concurrent bevacizumab use must be determined prior to randomization at cycle 2.
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
- Triple (Participant, Care Provider, Investigator)
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
- 未提供
排除标准
- •Participant has mucinous, germ cell, transitional cell, or undifferentiated tumor.
- •Participant has low-grade or Grade 1 epithelial ovarian cancer.
- •Participant has not adequately recovered from prior major surgery.
- •Participant is pregnant or is expecting to conceive children while receiving study drug or for up to 180 days after the last dose of study drug. Participant is breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose of study drug (women should not breastfeed or store breastmilk for use, during niraparib treatment and for 30 days after receiving the final dose of study treatment).
- •Participant has known active central nervous system metastases, carcinomatous meningitis, or both.
- •Participant has clinically significant cardiovascular disease.
- •Participant has a bowel obstruction by clinical symptoms or computed tomography (CT) scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess.
- •Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- •Participant has been diagnosed and/or treated with any therapy for invasive cancer <5 years from study enrollment, completed adjuvant chemotherapy and/or targeted therapy (example, trastuzumab) less than 3 years from enrollment, or completed adjuvant hormonal therapy less than 4 weeks from enrollment.
- •Participants with definitively treated non-invasive malignancies such as cervical carcinoma in situ, ductal carcinoma in situ, Grade 1 or 2, Stage I endometrial cancer, or non-melanomatous skin cancer are allowed.
- •Participant is at increased bleeding risk due to concurrent conditions (example, major injuries or major surgery within the past 28 days prior to start of study treatment and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
- •Participant is immunocompromised.
- •Participant has known active hepatitis B (example, hepatitis B surface antigen reactive) or hepatitis C (example, hepatitis C virus ribonucleic acid [qualitative] is detected).
- •Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or uncontrolled infection.
- •Participant has had investigational therapy administered within 4 weeks or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
- •Participant has received a live vaccine within 14 days of planned start of study therapy. Seasonal influenza vaccines that do not contain live viruses are allowed.
- •Participant has a known contraindication or uncontrolled hypersensitivity to the components of paclitaxel, carboplatin, niraparib, bevacizumab, dostarlimab, or their excipients.
- •Prior treatment for high-grade nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer (immunotherapy, anti-cancer therapy, radiation therapy).
- •Participant has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (example, thyroid hormone or insulin).
- •Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
研究组 & 干预措施
Participants receiving SOC+placebo
Participants in this arm will receive SOC (carboplatin+paclitaxel+/-bevacizumab) in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment with dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/-bevacizumab along with niraparib placebo and dostarlimab placebo
干预措施: Standard of care (Drug)
Participants receiving SOC+placebo
Participants in this arm will receive SOC (carboplatin+paclitaxel+/-bevacizumab) in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment with dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/-bevacizumab along with niraparib placebo and dostarlimab placebo
干预措施: Dostarlimab-Placebo (Drug)
Participants receiving SOC+placebo
Participants in this arm will receive SOC (carboplatin+paclitaxel+/-bevacizumab) in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment with dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/-bevacizumab along with niraparib placebo and dostarlimab placebo
干预措施: Niraparib-Placebo (Drug)
Participants receiving SOC+niraparib
Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/- bevacizumab with niraparib and dostarlimab placebo
干预措施: Niraparib (Drug)
Participants receiving SOC+niraparib
Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/- bevacizumab with niraparib and dostarlimab placebo
干预措施: Standard of care (Drug)
Participants receiving SOC+niraparib
Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/- bevacizumab with niraparib and dostarlimab placebo
干预措施: Dostarlimab-Placebo (Drug)
Participants receiving SOC+dostarlimab+niraparib
Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of +/-bevacizumab with niraparib and dostarlimab
干预措施: Niraparib (Drug)
Participants receiving SOC+dostarlimab+niraparib
Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of +/-bevacizumab with niraparib and dostarlimab
干预措施: Dostarlimab (TSR-042) (Drug)
Participants receiving SOC+dostarlimab+niraparib
Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of +/-bevacizumab with niraparib and dostarlimab
干预措施: Standard of care (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to approximately 316 weeks
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documented progressive disease (PD) or death due to any cause, whichever occurs first by the Investigator assessment according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeter (mm).
次要结局
- Overall Survival (OS)(Up to approximately 316 weeks)
- PFS Determined by Blinded Independent Central Review (BICR) Per RECIST v1.1 Criteria(Up to approximately 316 weeks)
- Time to First Subsequent Therapy (TFST)(Up to approximately 316 weeks)
- Time to Second Subsequent Therapy (TSST)(Up to approximately 316 weeks)
- Time to Second Progression (PFS2)(Up to approximately 316 weeks)
- Objective Response Rate (ORR)(Up to approximately 316 weeks)
- Duration of Response (DOR)(Up to approximately 316 weeks)
- Disease Control Rate (DCR)(Up to approximately 316 weeks)
- Number of Participants With Treatment Emergent Positive Antidrug Antibodies (ADAs) of Dostarlimab(Up to approximately 316 weeks)
- Change From Baseline (CFB) for the Visual Analogue Score (VAS) and Health Utility Index (HUI) of European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Questionnaire(Day1 of Chemo Cycles 2(baseline), 4&6; Day1 of Maintenance Cycles 1,2,3,6,9,12,15,17,23,29,35,41,47,53,59,65,71,77,83,89; EOT visit up to a maximum of 63 months; LTFU visit up to a maximum of 69 months(including SFU visit up to a maximum of 61 months))
- Number of Participants With Improvement and Worsening in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30)(Day1 of Chemo Cycles 2(baseline), 4&6; Day1 of Maintenance Cycles 1,2,3,6,9,12,15,17,23,29,35,41,47,53,59,65,71,77,83,89; EOT visit up to a maximum of 63 months; LTFU visit up to a maximum of 69 months(including SFU visit up to a maximum of 61 months))
- Number of Participants With Change in Status in EORTC-QLQ Ovarian Cancer Module (EORTC-QLQ-OV28) Questionnaire(Day1 of Chemo Cycles 2(baseline), 4&6; Day1 of Maintenance Cycles 1,2,3,6,9,12,15,17,23,29,35,41,47,53,59,65,71,77,83,89; EOT visit up to a maximum of 63 months; LTFU visit up to a maximum of 69 months(including SFU visit up to a maximum of 61 months))