A Phase 2 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients With Platinum-Resistant Ovarian Cancer (MOONSTONE)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Tesaro, Inc.
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
研究概览
简要总结
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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 who experienced disease progression within 3 months (12 weeks or 84 days) of first-line platinum therapy.
- •Participants with a known deleterious or suspected BRCA 1 or 2 mutation.
- •Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
- •Participant has received prior therapy with a PARP-1/PARP-2 inhibitor.
- •Participant has a known hypersensitivity to dostarlimab (TSR-042), Niraparib, their components, or their excipients.
- •Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia.
- •Participant has not recovered from prior chemotherapy induced adverse events.
- •Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- •Participant is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
- •Participant has received prior systemic anticancer therapy including cytotoxic chemotherapy, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment.
- •Participant has received live vaccine within 14 days of planned start of study therapy
- •Participant has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels participant symptoms are not symptomatic, participants can undergo a scan to confirm for eligibility).
- •Participant had major surgery with 4 weeks of starting the first dose of the study treatment or participant has not recovered from any effects of any major surgery.
- •Participant has a known additional malignancy that progressed or required active treatment within the last 2 years.
- •Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active controlled infection.
- •Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
- •Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
- •Participant with a known history of human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
- •Cluster of differentiation 4 >=350/microliter (μL) and viral load <400 copies/milliliter (mL)
- •No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
- •No history of HIV-associated malignancy for the past 5 years
- •Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started >4 weeks prior to study enrollment
- •Participant is immunocompromised. Participants with splenectomy are allowed.
- •Participant has an ongoing bowel obstruction or has other conditions that would lead to impaired absorption of oral niraparib.
- •Participant has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
研究组 & 干预措施
Niraparib+Dostarlimab (TSR-042)
Participants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight <77 kg or platelet count <150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months.
干预措施: Niraparib (Drug)
Niraparib+Dostarlimab (TSR-042)
Participants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight <77 kg or platelet count <150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months.
干预措施: Dostarlimab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
时间窗: Up to approximately 22 months
ORR is defined as the percentage of participants who have achieved confirmed complete response (CR) or partial response (PR), as determined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria based on Investigator assessment and computed tomography (CT) scans were commonly used for tumor imaging.
ORR in Participants With PROC Who Have Programmed Cell Death-ligand 1 (PD-L 1) Positive Status
时间窗: Up to approximately 22 months
ORR is defined as the percentage of participants who have achieved confirmed CR or PR, as determined by RECIST v1.1 criteria based on Investigator assessment and CT scans were commonly used for tumor imaging. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with combined positive score (vCPS) \>=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
次要结局
- DOR in Participants With PROC Based on IRC Assessment(Up to approximately 22 months)
- DOR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment(Up to approximately 22 months)
- Progression-free Survival (PFS) in Participants With PROC(Up to approximately 22 months)
- Overall Survival (OS) in Participants With PROC(Up to approximately 22 months)
- PFS in Participants With PROC Based on IRC Assessment(Up to approximately 22 months)
- ORR in Participants With PROC Based on Independent Review Committee (IRC) Assessment(Up to approximately 22 months)
- ORR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment(Up to approximately 22 months)
- Change in Baseline in Activated Partial Thromboplastin Time(Baseline and up to approximately 27 months)
- Change From Baseline in Thyrotropin(Baseline and up to approximately 27 months)
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs) and Adverse Event of Special Interest (AESI)(Up to approximately 27 months)
- Duration of Response (DOR) in Participants With PROC(Up to approximately 22 months)
- DOR in Participants With PROC Who Have PD-L 1 Positive Status(Up to approximately 22 months)
- PFS in Participants With PROC Who Have PD-L 1 Positive Status(Up to approximately 22 months)
- OS in Participants With PROC Who Have PD-L 1 Positive Status(Up to approximately 22 months)
- Disease Control Rate (DCR) in Participants With PROC(Up to approximately 22 months)
- DCR in Participants With PROC Who Have PD-L 1 Positive Status(Up to approximately 22 months)
- PFS in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment(Up to approximately 22 months)
- DCR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment(Up to approximately 22 months)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Up to approximately 27 months)
- Change From Baseline in Pulse Rate(Up to approximately 27 months)
- Change From Baseline in Temperature(Up to approximately 27 months)
- Change From Baseline in Prothrombin International Normalized Ratio(Baseline and up to approximately 27 months)
- DCR in Participants With PROC Based on IRC Assessment(Up to approximately 22 months)
- Number of Participants With Grade Shift From Baseline in Hematology(Up to approximately 27 months)
- Number of Participants With Grade Shift From Baseline in Plasma Chemistry(Up to approximately 27 months)