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)
Overview
- Phase
- Phase 2
- Intervention
- Niraparib
- Conditions
- Ovarian Neoplasms
- Sponsor
- Tesaro, Inc.
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Niraparib
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.
Intervention: Dostarlimab
Outcomes
Primary Outcomes
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)