Symptoms and General Pathology

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Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

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Vasodilator Agents

Analgesics

Pembrolizumab

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Antibodies, Monoclonal

Niraparib

Dostarlimab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Adenosine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

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.

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.

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.

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).

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).

Niraparib is an orally available, potent, highly selective poly adenosine diphosphate- ribose (poly ADP-ribose) polymerase-1 (PARP-1) and PARP-2 inhibitor. It will be available as 100 milligrams (mg) capsules and will be administered as 2 X 100 mg capsules (200 mg per day) orally once daily (QD).

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G-4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands (PD-L1 and PD-L2). It will be available as 50 mg lyophilized powder single-use vials or 100 mg/4 milliliters (mL) (25 mg/mL) solution in a single-dose vial. It will be administered at a dose of 200 mg intravenous (IV) using a 30-minute IV infusion

TSR-042 (Dostarlimab) is a humanized mAb of the IgG4/kappa isotype that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. It will be administered at a dose of 500 mg for every 3 weeks (Q3W) for first 4 cycles followed by 1000 mg for every 6 weeks (Q6W) for all subsequent cycles using a 30-minute IV infusion. TSR-042 (dostarlimab) will be supplied as a solution of 160 mg (20 mg/mL) or 500 mg (50 mg/mL) in a single-dose vial.

TSR-042 (Dostarlimab)

GSK Clinical Trials

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).

Participants will receive niraparib either as monotherapy or in combination with pembrolizumab during Stage 1 of the study. Participants will receive niraparib in combination with TSR-042 (dostarlimab) during Stage 2 of the study.

Effects of Single Agent Niraparib and Niraparib Plus Programmed Cell Death-1 (PD-1) Inhibitors in Non-Small Cell Lung Cancer Participants

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

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Overall survival was defined as the time from date of first dose to the date of death due to any cause.

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.

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.

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.

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.

An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events

An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events

An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.

An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.

Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter (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.

Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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.

Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.

Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.

Blood samples were collected at indicated time points.

Tesaro, Inc.

Safety Population comprised of participants who received at least one dose of either study medication. Data was not collected for Cohort 2A-Stage 2 as no participant was enrolled in this Cohort.

Participants with locally advanced and metastatic non-small cell lung cancer (NSCLC) (all histologies) with no prior systemic chemotherapy or programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor treatment and whose tumors had high PD-L1 expression (tumor proportion score \[TPS\]: \>= 50 percent \[%\]) received a combination of niraparib and pembrolizumab. Niraparib was given at a dose of 200 milligrams (mg) orally once daily during each 21-day cycle. Pembrolizumab was administered as an intravenous (IV) infusion at a dose of 200 mg on Day 1 of each 21-day cycle.

Stage 1 (Cohort 1): Niraparib + 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 had PD-L1 expression (TPS: 1% to 49%) received a combination of niraparib and pembrolizumab. Niraparib was given at a dose of 200 mg orally once daily during each 21-day cycle. Pembrolizumab was administered as an IV infusion at a dose of 200 on Day 1 of each 21-day cycle.

Stage 1 (Cohort 2): Niraparib + Pembrolizumab

Participants with locally advanced and metastatic squamous NSCLC who were previously treated with both platinum and either PD-1 or PD-L1 inhibitor received single agent niraparib at a dose of 200 mg orally once daily during each 21-day cycle.

Stage 1 (Cohort 3): Niraparib

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%) received a combination of niraparib and TSR-042 (Dostarlimab). Niraparib was given at a dose of 200 mg orally once daily during each 21-day cycle. TSR-042 (Dostarlimab) was administered as an IV infusion at a dose of 500 mg once every 3 weeks for first 4 cycles followed by 1000 mg dose once every 6 weeks for subsequent cycles (each cycle of 21 days).

Stage 2 (Cohort 1A): Niraparib + 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%) were planned to receive a combination of niraparib and TSR-042 (Dostarlimab). Niraparib was planned to be given at a dose of 200 mg orally once daily. TSR-042 (Dostarlimab) was planed to be administered as an IV infusion at a dose of 500 mg once every 3 weeks for first 4 cycles followed by 1000 mg dose once every 6 weeks for all subsequent cycles (each cycle of 21 days).

Stage 2 (Cohort 2A): Niraparib + 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%) were planned to receive a combination of niraparib and TSR-042 (Dostarlimab). Niraparib was planned to be given at a dose of 200 mg orally once daily. TSR-042 (Dostarlimab) was planned to be administered as an IV infusion at a dose of 500 mg once every 3 weeks for first 4 cycles followed by 1000 mg dose once every 6 weeks for all subsequent cycles (each cycle of 21 days).

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Data was not collected for Cohort 2A of Stage 2 as no participant was enrolled into this Cohort of the study. Safety Population comprised of participants who received at least one dose of either study medications.

GSK Response Center

Modified intent-to-treat (mITT) Population comprised of all participants who received any study drug and did not withdraw consent prior to having at least one post-Baseline tumor assessment.

Stage 1: Cohort 1: Objective Response Rate (ORR)

Stage 1: Cohort 2: Objective Response Rate

Stage 1: Cohort 3: Objective Response Rate

mITT Population. Data was not collected for Cohort 2A of Stage 2 as no participant was enrolled into this Cohort of the study.

Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate

Any SAE

Any non-SAE

Safety Population comprised of participants who received at least one dose of either study medications.

Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs

Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs

Safety Population. Data was not collected for Cohort 2A of Stage 2 as no participant was enrolled into this Cohort of the study.

Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs

Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs

Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs

Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs

Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs

mITT Population. Only those participants with confirmed response were analyzed.

Stage 1: Cohort 1: Duration of Response

Stage 1: Cohort 2: Duration of Response

mITT Population. No participant had confirmed response. Hence, data for duration of response was not collected.

Stage 1 : Cohort 3: Duration of Response

mITT Population. Only those participants with confirmed response were analyzed. Data was not collected for Cohort 2A of Stage 2 as no participant was enrolled into this Cohort of the study.

Stage 2: Cohorts 1A and 2A: Duration of Response

Stage 1 : Cohort 1: Disease Control Rate

Stage 1 : Cohort 2: Disease Control Rate

Stage 1 : Cohort 3: Disease Control Rate

Stage 2: Cohorts 1A and 2A: Disease Control Rate

Stage 1 : Cohort 1: Progression-free Survival

Stage 1 : Cohort 2: Progression-free Survival

Stage 1 : Cohort 3: Progression-free Survival

Stage 2: Cohorts 1A and 2A: Progression-free Survival

Cycle 1 Day 1; Pre-dose

Cycle 1 Day 1; 30 Minutes Post-dose

Cycle 1 Day 1; 1 Hour Post-dose

Cycle 1 Day 1; 2 Hours Post-dose

Cycle 1 Day 1; 4 Hours Post-dose

Cycle 1 Day 1; 8 Hours Post-dose

Cycle 1 Day 1; 96 Hours Post-dose

Cycle 1 Day 1; 168 Hours Post-dose

Cycle 2; Pre-dose

Cycle 2; 4 Hours Post-dose

Cycle 4; Pre-dose

Cycle 4; 4 Hours Post-dose

Cycle 8; Pre-dose

Cycle 8; 4 Hours Post-dose

Pharmacokinetic Population comprised of participants who had at least one of measurable niraparib concentration. Only those participants with data available at specified time points were analyzed.

Stage 1: Cohort 1: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab

Cycle 1 Day 1; 24 Hours Post-dose

Cycle 1 Day 1; 336 Hours Post-dose

Cycle 4; 30 Minutes Post-dose

Cycle 4; 1 Hour Post-dose

Cycle 4; 2 Hours Post-dose

Cycle 4; 8 Hours, Post-dose

Cycle 4; 24 Hours Post-dose

Cycle 4; 96 Hours

Cycle 4; 168 Hours

Cycle 4; 336 Hours

Cycle 8; 4 Hours post-dose

Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed.

Stage 1: Cohort 2: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab

Stage 1: Cohort 3: Plasma Concentration of Niraparib Following Niraparib Monotherapy

Cycle 9; Pre-dose

Cycle 9; 4 Hours Post-dose

Pharmacokinetic Population. Data was not collected for Cohort 2A of Stage 2 as no participant was enrolled into this Cohort of the study. Only those participants with data available at specified time points were analyzed.

Stage 2: Cohorts 1A and 2A: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and TSR-042 (Dostarlimab)

mITT Population. OS was removed as a secondary endpoint through a protocol amendment, following completion of the primary endpoint. OS will not be analyzed and reported for this study.

Spots Global Cancer Trial Database for Effects of Single Agent Niraparib and Niraparib Plus Programmed Cell Death-1 (PD-1) Inhibitors in Non-Small Cell Lung Cancer Participants

Trial Identification

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Study Description

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