Phase 2, Multi-Arm Study of Niraparib Administered Alone and in Combination With a PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Niraparib
- Conditions
- Neoplasms
- Sponsor
- Tesaro, Inc.
- Enrollment
- 53
- Locations
- 1
- Primary Endpoint
- Stage 1: Cohort 1: Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of niraparib alone and in combination with PD-1 inhibitors in participants with locally advanced and metastatic non-small cell lung cancer (NSCLC). The study will consist of 2 stages. In stage 1, participants from Cohorts 1 and 2 will receive niraparib plus PD-1 inhibitor; pembrolizumab and participants from Cohort 3 will receive niraparib alone. In Stage 2, participants from Cohorts 1A and 2A will receive niraparib plus the PD-1 inhibitor, TSR-042 (Dostarlimab).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female participants at least 18 years of age.
- •Histological or cytological proven advanced (unresectable) or metastatic NSCLC as defined as stage IIIB (positive supraclavicular lymph nodes) not amenable to definitive chemoradiotherapy or stage IV NSCLC.
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate organ function, defined as:
- •Absolute neutrophil count (ANC) \>= 1500 per microliter (/µL).
- •Platelets \>= 100,000/µL.
- •Hemoglobin \>= 9 grams per deciliter (g/dL) or \>= 5.6 millimoles per liter (mmol/L).
- •Serum creatinine \<= 1.5 times upper limit of normal (ULN) or creatinine clearance \>= 50 milliliters per minute (mL/min) (as calculated using the Cockcroft Gault equation or measured using 24-hour urine creatinine clearance) for participants with creatinine levels \> 1.5 times institutional ULN.
- •Total bilirubin \<= 1.5 times ULN except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin \<= 1.5 times ULN of the direct bilirubin.
Exclusion Criteria
- Not provided
Arms & Interventions
Stage 1 (Cohort 1): Niraparib plus Pembrolizumab
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/programmed death-ligand 1 (PD-L1) inhibitor treatment and whose tumors have high PD-L1 expression (tumor proportion score \[TPS\]: \>= 50 percent \[%\]) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.
Intervention: Niraparib
Stage 1 (Cohort 1): Niraparib plus Pembrolizumab
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/programmed death-ligand 1 (PD-L1) inhibitor treatment and whose tumors have high PD-L1 expression (tumor proportion score \[TPS\]: \>= 50 percent \[%\]) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.
Intervention: Pembrolizumab
Stage 1 (Cohort 2): Niraparib plus Pembrolizumab
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.
Intervention: Niraparib
Stage 1 (Cohort 2): Niraparib plus Pembrolizumab
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.
Intervention: Pembrolizumab
Stage 1 (Cohort 3): Niraparib
Participants with locally advanced and metastatic squamous NSCLC who have been previously treated with both platinum and either PD-1 or PD-L1 inhibitor will receive single agent niraparib.
Intervention: Niraparib
Stage 2 (Cohort 1A): Niraparib plus TSR-042 (Dostarlimab)
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have high PD-L1 expression (TPS: \>= 50%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).
Intervention: Niraparib
Stage 2 (Cohort 1A): Niraparib plus TSR-042 (Dostarlimab)
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have high PD-L1 expression (TPS: \>= 50%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).
Intervention: TSR-042 (Dostarlimab)
Stage 2 (Cohort 2A): Niraparib plus TSR-042 (Dostarlimab)
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).
Intervention: Niraparib
Stage 2 (Cohort 2A): Niraparib plus TSR-042 (Dostarlimab)
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).
Intervention: TSR-042 (Dostarlimab)
Outcomes
Primary Outcomes
Stage 1: Cohort 1: Objective Response Rate (ORR)
Time Frame: Up to a maximum of 29 months
ORR is the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Data has been presented for participants with NSCLC whose tumors have high PD-L1 expression (TPS\>=50%). Confidence interval was calculated using binomial exact method.
Stage 1: Cohort 2: Objective Response Rate
Time Frame: Up to a maximum of 17 months
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Data has been presented for participants with NSCLC having PD-L1 expression in tumors (TPS: 1 to 49%). Confidence interval was calculated using binomial exact method.
Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate
Time Frame: Up to a maximum of 17 months
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Stage 1: Cohort 3: Objective Response Rate
Time Frame: Up to a maximum of 6 months
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Data is presented for participants with locally advanced and metastatic squamous NSCLC. Confidence interval was calculated using binomial exact method.
Secondary Outcomes
- Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs(Up to a maximum of 6 months)
- Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs(Up to a maximum of 45 months)
- Stage 2: Cohorts 1A and 2A: Disease Control Rate(Up to a maximum of 29 months)
- Stage 1 : Cohort 2: Progression-free Survival(Up to a maximum of 17 months)
- Stage 1: Cohort 1: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab(Cycle 1 Day 1(Pre-dose and 30 Minutes, 1 Hour, 2 Hours, 4 Hours, 8 Hours, 96 Hours, 168 Hours Post-dose); Cycles 2, 4, 8 (Pre-dose and 4 Hours Post-dose) (each cycle of 21 days))
- Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs(Up to a maximum of 17 months)
- Stage 1 : Cohort 3: Disease Control Rate(Up to a maximum of 6 months)
- Stage 1 : Cohort 3: Progression-free Survival(Up to a maximum of 6 months)
- Stage 1: Cohort 2: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab(Cycle 1 Day 1 (Pre-dose and 30 Minutes, 1, 2, 4, 8, 24, 168, 336 Hours Post-dose), Cycles 2, 8 (Pre-dose and 4 Hours Post-dose), Cycle 4 (Pre-dose and 30 Minutes, 1, 2, 4, 8, 24, 96, 168, 336 Hours Post-dose) (each cycle of 21 days))
- Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)(Up to a maximum of 45 months)
- Stage 2: Cohorts 1A and 2A: Duration of Response(Up to a maximum of 29 months)
- Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs(Up to a maximum of 17 months)
- Stage 1: Cohort 1: Duration of Response(Up to a maximum of 45 months)
- Stage 1 : Cohort 1: Disease Control Rate(Up to a maximum of 45 months)
- Stage 1 : Cohort 2: Disease Control Rate(Up to a maximum of 17 months)
- Stage 1 : Cohort 1: Progression-free Survival(Up to a maximum of 45 months)
- Stage 2: Cohorts 1A and 2A: Progression-free Survival(Up to a maximum of 29 months)
- Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs(Up to a maximum of 29 months)
- Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs(Up to a maximum of 6 months)
- Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs(Up to maximum 29 months)
- Stage 1: Cohort 2: Duration of Response(Up to a maximum of 17 months)
- Stage 1 : Cohort 3: Duration of Response(Up to a maximum of 6 months)
- Stage 1: Cohort 3: Plasma Concentration of Niraparib Following Niraparib Monotherapy(Cycle 1 Day 1 (Pre-dose and 4 Hours Post-dose), Cycles 2, 4 and 8 (Pre-dose and 4 Hours Post-dose) (each cycle of 21 days))
- Stage 2: Cohorts 1A and 2A: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and TSR-042 (Dostarlimab)(Cycle 1 Day 1 (Pre-dose and 4 Hours Post-dose), Cycles 2, 4 and 9 (Pre-dose and 4 Hours Post-dose) (each cycle of 21 days))