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

Sponsor

Tesaro, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03308942

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Niraparib Biological: Pembrolizumab Biological: TSR-042 (Dostarlimab)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Masking Description:

This will be an open-label study.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 29, 2017

Actual Primary Completion Date :

May 4, 2020

Actual Study Completion Date :

Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Niraparib 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). Biological: Pembrolizumab 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
Experimental: 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.	Drug: Niraparib 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). Biological: Pembrolizumab 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
Experimental: 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.	Drug: Niraparib 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).
Experimental: 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).	Drug: Niraparib 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). Biological: TSR-042 (Dostarlimab) 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.
Experimental: 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).	Drug: Niraparib 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). Biological: TSR-042 (Dostarlimab) 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.

Outcome Measures

Primary Outcome Measures

Stage 1: Cohort 1: Objective Response Rate (ORR) [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 [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 1: Cohort 3: Objective Response Rate [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.
Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate [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.

Secondary Outcome Measures

Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [Up to a maximum of 29 months]
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. An 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.
Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs [Up to a maximum of 17 months]
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. An 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.
Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs [Up to a maximum of 6 months]
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. An 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.
Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs [Up to a maximum of 17 months]
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. An 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.
Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs [Up to a maximum of 29 months]
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.
Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs [Up to a maximum of 17 months]
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.
Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs [Up to a maximum of 6 months]
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.
Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs [Up to maximum 17 months]
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.
Stage 1: Cohort 1: Duration of Response [Up to a maximum of 29 months]
Duration of Response is 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.
Stage 1: Cohort 2: Duration of Response [Up to a maximum of 17 months]
Duration of Response is 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.
Stage 1 : Cohort 3: Duration of Response [Up to a maximum of 6 months]
Duration of Response is 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.
Stage 2: Cohorts 1A and 2A: Duration of Response [Up to a maximum of 17 months]
Duration of Response is 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.
Stage 1 : Cohort 1: Disease Control Rate [Up to a maximum of 29 months]
Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or stable disease (SD) per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Stage 1 : Cohort 2: Disease Control Rate [Up to a maximum of 17 months]
Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Stage 1 : Cohort 3: Disease Control Rate [Up to a maximum of 6 months]
Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Stage 2: Cohorts 1A and 2A: Disease Control Rate [Up to a maximum of 17 months]
Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Stage 1 : Cohort 1: Progression-free Survival [Up to a maximum of 29 months]
Progression-free survival is 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 is 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.
Stage 1 : Cohort 2: Progression-free Survival [Up to a maximum of 17 months]
Progression-free survival is 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 is 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.
Stage 1 : Cohort 3: Progression-free Survival [Up to a maximum of 6 months]
Progression-free survival is 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 is 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.
Stage 2: Cohorts 1A and 2A: Progression-free Survival [Up to a maximum of 17 months]
Progression-free survival is 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 is 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.
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)]
Blood samples were collected at indicated time points.
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)]
Blood samples were collected at indicated time points.
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)]
Blood samples were collected at indicated time points.
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)]
Blood samples were collected at indicated time points.

Other Outcome Measures

Stage 1: Cohort 1: Overall Survival (OS) [Up to a maximum of 29 months]
Overall survival
Stage 1: Cohort 2: Overall Survival [Up to a maximum of 17 months]
Overall survival
Stage 1: Cohort 3: Overall Survival [Up to a maximum of 6 months]
Overall survival
Stage 2: Cohorts 1A and 2A: Overall Survival [Up to a maximum of 17 months]
Overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

General 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) 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 times ULN unless liver metastases are present, in which case they must be <= 5 times ULN.

Participant must have recovered to Grade 1 toxicity from prior cancer therapy (a participant with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
Participant agrees to submit formalin fixed paraffin embedded (FFPE) tumor tissue specimen, which may have been collected at any time prior to screening. If no archival FFPE tumor tissue is available, participant agrees to undergo a tumor tissue biopsy before Cycle 1/Day 1. (For Cohort 3 only: if diagnosis was made by cytology and archival tissue is not available, participant will not need to provide tumor tissue).
Participants is able to take oral medications.
Female participant meets the following criteria:

Female participant (of childbearing potential) is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug, and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment or is of nonchildbearing potential; or b) Female participant is of nonchildbearing potential, other than medical reasons, defined as follows: i) >=45 years of age and has not had menses for > 1 year. ii) Amenorrheic for < 2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone (FSH) value in the postmenopausal range upon screening evaluation.

Post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the participant must be willing to use 2 highly effective contraception methods throughout the study, starting with the screening visit through 180 days after the last dose of study therapy.

Male participant agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Participant is able to understand the study procedures and agree to participate in the study by providing written informed consent.

Cohort Specific Inclusion Criteria:

Cohorts 1 and 1A (combination of niraparib and PD-1 inhibitor): participants must have tumors with high PD-L1 expression (TPS >= 50%) per local assessment; with no known Epidermal Growth Factor Receptor (EGFR)-sensitizing mutation and/or ROS -1 or anaplastic lymphoma kinase (ALK) translocation, and no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC.
Cohorts 2 and 2A (combination of niraparib and PD-1 inhibitor): participants must have tumors with PD-L1 expression (TPS between 1% and 49%) per local assessment, with no known EGFR-sensitizing mutation and/or ROS-1 or ALK translocation, and no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC.
Cohort 3 (single agent niraparib): participants must have metastatic squamous non-small cell lung cancer (sqNSCLC) and have progressed after both prior platinum-based chemotherapy and prior PD-1 or PD-L1 inhibitor treatment.

Exclusion Criteria for Cohorts 1, 1A , 2 and 2A:

Participant has received systemic therapy for the treatment of advanced stage NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Known hypersensitivity to the components of niraparib, pembrolizumab, TSR-042 (Dostarlimab), or their excipients.
Known EGFR (exon 19 and 21) mutations, ALK translocations, and/or ROS-1 translocations.
Participant has a history or current condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the participant's participation for the full duration of the study treatment.
Known diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
Participant is immunocompromised, in the opinion of the Investigator.
Current participation in a treatment study or past participation in a study of an investigational agent within 4 weeks before the first dose of study treatment.
Symptomatic uncontrolled brain or leptomeningeal metastases. (To be considered "controlled," central nervous system [CNS] disease must have undergone treatment [example, radiation or chemotherapy] at least 1 month prior to study entry. The participant must not have any new or progressive signs or symptoms related to the CNS disease and must be taking <= 10 mg of prednisone or equivalent per day or no steroids.) Participants who have untreated brain metastases and who are not symptomatic may enroll if the Investigator feels that treatment of these metastases is not indicated. A scan to confirm the absence of brain metastases is not required. Participants with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically SD for 28 days.
Active autoimmune disease that required systemic treatment in the past 2 years (with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (examples, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
Major surgery within 3 weeks of starting the study or participant has not recovered from any effects of any major surgery.
Other active concomitant malignancy that warrants systemic therapy.
Poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, uncontrolled hypertension, active uncontrolled coagulopathy or any psychiatric disorder that prohibits obtaining informed consent.
Known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment.
Participant is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for 180 days (for pregnancy or conception) or 30 days (for breastfeeding) after the last dose of study treatment.
Male participant is expecting to donate sperm or father children while receiving study drug or for 120 days after the last dose of study treatment.
Known active hepatic disease (known hepatic cirrhosis, hepatitis B surface antigen-positive status, or suspected active hepatitis C infection).
Prior treatment with a known poly adenosine diphosphate-ribose (ADP-ribose) polymerase (PARP) inhibitor.
Participant received a live vaccine within 30 days of planned start of study therapy.
Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Exclusion criteria for Cohort 3:

Platinum-treated participant who progressed while on or within less than 8 weeks from the last day of platinum administration.
Known hypersensitivity to the components of niraparib or excipients.
Participant has a history or current condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the participant's participation for the full duration of the study treatment.
Known diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
Current participation in a treatment study or past participation in a study of an investigational agent within 4 weeks before the first dose of study treatment.
Symptomatic uncontrolled brain or leptomeningeal metastases. (To be considered "controlled," CNS disease must have undergone treatment [example, radiation or chemotherapy] at least 1 month prior to study entry. The participant must not have any new or progressive signs or symptoms related to the CNS disease and must be taking <= 10 mg of prednisone or equivalent per day or no steroids.) Participants who have untreated brain metastases and who are not symptomatic may enroll if the investigator feels that treatment of these metastases is not indicated. A scan to confirm the absence of brain metastases is not required. Participants with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically SD for 28 days.
Major surgery within 3 weeks of starting the study or participant has not recovered from any effects of any major surgery.
Other active concomitant malignancy that warrants systemic therapy.
Poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, uncontrolled hypertension, active uncontrolled coagulopathy, or any psychiatric disorder that prohibits obtaining informed consent.
Known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment.
Participant is pregnant, breastfeeding, or expecting to conceive children, while receiving study treatment and for 180 days (for pregnancy or conception) or 30 days (for breastfeeding) after the last dose of study treatment.
Male participant is expecting to donate sperm or father children while receiving study drug or for 120 days after the last dose of study treatment.
Participant is immunocompromised, in the opinion of the Investigator.
Known active hepatic disease (known hepatic cirrhosis, hepatitis B surface antigen-positive status, or suspected active hepatitis C infection).
Prior treatment with a known PARP inhibitor.
Known history of MDS or AML.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Whittier	California	United States	90603
2	GSK Investigational Site	Port Saint Lucie	Florida	United States	34952
3	GSK Investigational Site	Atlanta	Georgia	United States	30322
4	GSK Investigational Site	Harvey	Illinois	United States	60426
5	GSK Investigational Site	Tinley Park	Illinois	United States	60487
6	GSK Investigational Site	Boston	Massachusetts	United States	02215
7	GSK Investigational Site	Morristown	New Jersey	United States	07962-1956
8	GSK Investigational Site	Buffalo	New York	United States	14263
9	GSK Investigational Site	Durham	North Carolina	United States	27710
10	GSK Investigational Site	Canton	Ohio	United States	44718
11	GSK Investigational Site	Cleveland	Ohio	United States	44106
12	GSK Investigational Site	Columbus	Ohio	United States	31904
13	GSK Investigational Site	Toledo	Ohio	United States	43623
14	GSK Investigational Site	Nashville	Tennessee	United States	37203
15	GSK Investigational Site	Kennewick	Washington	United States	99336
16	GSK Investigational Site	Tacoma	Washington	United States	98405

Sponsors and Collaborators

Tesaro, Inc.

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Tesaro, Inc.

ClinicalTrials.gov Identifier:

NCT03308942

Other Study ID Numbers:

213352
3000-02-001

First Posted:

Oct 13, 2017

Last Update Posted:

Oct 21, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Tesaro, Inc.

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Pembrolizumab

Niraparib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled across 26 centers in the United States. This study consisted of two stages; Stage 1 (Cohorts 1, 2, 3) and Stage 2 (Cohorts 1A, 2A). The results presented are based on the Primary analysis up to a data cut-off date: 04-May-2020. Additional results will be provided after study completion.
Pre-assignment Detail	A total of 69 participants were screened, of which 16 failed screening and 53 participants (41 in Stage 1 and 12 in Stage 2) were enrolled into the study. Data was not collected for Cohort 2A of Stage 2 as the Sponsor decided not to open this Cohort to enrollment.

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab	Stage 1 (Cohort 2): Niraparib + Pembrolizumab	Stage 1 (Cohort 3): Niraparib	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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.	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.	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.	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).	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).
Period Title: Stage 1 (up to a Maximum of 29 Months)
STARTED	17	21	3	0	0
COMPLETED	0	0	0	0	0
NOT COMPLETED	17	21	3	0	0
Period Title: Stage 1 (up to a Maximum of 29 Months)
STARTED	0	0	0	12	0
COMPLETED	0	0	0	0	0
NOT COMPLETED	0	0	0	12	0

Baseline Characteristics

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab	Stage 1 (Cohort 2): Niraparib + Pembrolizumab	Stage 1 (Cohort 3): Niraparib	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)	Total
Arm/Group Description	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.	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.	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.	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).	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 of all reporting groups
Overall Participants	17	21	3	12	0	53
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.1 (7.55)	70.9 (9.78)	72.3 (10.69)	68.3 (6.74)	70.1 (8.35)
Sex: Female, Male (Count of Participants)
Female	6 35.3%	12 57.1%	0 0%	6 50%	24 Infinity
Male	11 64.7%	9 42.9%	3 100%	6 50%	29 Infinity
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 8.3%	1 Infinity
Asian	0 0%	1 4.8%	0 0%	1 8.3%	2 Infinity
Black or African American	1 5.9%	0 0%	0 0%	2 16.7%	3 Infinity
White	14 82.4%	19 90.5%	3 100%	8 66.7%	44 Infinity
Unknown	2 11.8%	1 4.8%	0 0%	0 0%	3 Infinity

Outcome Measures

1. Primary Outcome

Title	Stage 1: Cohort 1: Objective Response Rate (ORR)
Description	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.
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	16
Number (95% Confidence Interval) [Percentage of participants]	56.3 331.2%

2. Primary Outcome

Title	Stage 1: Cohort 2: Objective Response Rate
Description	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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	20
Number (95% Confidence Interval) [Percentage of participants]	20.0 117.6%

3. Primary Outcome

Title	Stage 1: Cohort 3: Objective Response Rate
Description	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.
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	2
Number (95% Confidence Interval) [Percentage of participants]	0 0%

4. Primary Outcome

Title	Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate
Description	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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

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

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	11	0
Number (95% Confidence Interval) [Percentage of participants]	9.1 53.5%

5. Secondary Outcome

Title	Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Description	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. An 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.
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

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

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	17
Any SAE	11 64.7%
Any non-SAE	17 100%

6. Secondary Outcome

Title	Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs
Description	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. An 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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	21
Any SAE	14 82.4%
Any non-SAE	20 117.6%

7. Secondary Outcome

Title	Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs
Description	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. An 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.
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	3
Any SAE	1 5.9%
Any non-SAE	3 17.6%

8. Secondary Outcome

Title	Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs
Description	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. An 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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

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

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	12	0
Any SAE	7 41.2%
Any non-SAE	12 70.6%

9. Secondary Outcome

Title	Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs
Description	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.
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	17
Count of Participants [Participants]	10 58.8%

10. Secondary Outcome

Title	Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs
Description	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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	21
Count of Participants [Participants]	9 52.9%

11. Secondary Outcome

Title	Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs
Description	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.
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	3
Count of Participants [Participants]	1 5.9%

12. Secondary Outcome

Title	Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs
Description	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.
Time Frame	Up to maximum 17 months

Outcome Measure Data

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

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	12	0
Count of Participants [Participants]	2 11.8%

13. Secondary Outcome

Title	Stage 1: Cohort 1: Duration of Response
Description	Duration of Response is 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.
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

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

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	9
Median (Inter-Quartile Range) [Months]	19.7

14. Secondary Outcome

Title	Stage 1: Cohort 2: Duration of Response
Description	Duration of Response is 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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

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

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	4
Median (Inter-Quartile Range) [Months]	9.4

15. Secondary Outcome

Title	Stage 1 : Cohort 3: Duration of Response
Description	Duration of Response is 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.
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

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

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	0

16. Secondary Outcome

Title	Stage 2: Cohorts 1A and 2A: Duration of Response
Description	Duration of Response is 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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	1	0
Median (Inter-Quartile Range) [Months]	NA

17. Secondary Outcome

Title	Stage 1 : Cohort 1: Disease Control Rate
Description	Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or stable disease (SD) per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	16
Number (95% Confidence Interval) [Percentage of participants]	87.5 514.7%

18. Secondary Outcome

Title	Stage 1 : Cohort 2: Disease Control Rate
Description	Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	20
Number (95% Confidence Interval) [Percentage of participants]	70.0 411.8%

19. Secondary Outcome

Title	Stage 1 : Cohort 3: Disease Control Rate
Description	Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	2
Number (95% Confidence Interval) [Percentage of participants]	50.0 294.1%

20. Secondary Outcome

Title	Stage 2: Cohorts 1A and 2A: Disease Control Rate
Description	Disease Control Rate is defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

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

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	11	0
Number (95% Confidence Interval) [Percentage of participants]	54.5 320.6%

21. Secondary Outcome

Title	Stage 1 : Cohort 1: Progression-free Survival
Description	Progression-free survival is 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 is 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.
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	16
Median (Inter-Quartile Range) [Months]	8.4

22. Secondary Outcome

Title	Stage 1 : Cohort 2: Progression-free Survival
Description	Progression-free survival is 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 is 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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	20
Median (Inter-Quartile Range) [Months]	4.2

23. Secondary Outcome

Title	Stage 1 : Cohort 3: Progression-free Survival
Description	Progression-free survival is 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 is 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.
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	2
Median (Inter-Quartile Range) [Months]	4.0

24. Secondary Outcome

Title	Stage 2: Cohorts 1A and 2A: Progression-free Survival
Description	Progression-free survival is 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 is 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.
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

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

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	11	0
Median (Inter-Quartile Range) [Months]	4.4

25. Secondary Outcome

Title	Stage 1: Cohort 1: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab
Description	Blood samples were collected at indicated time points.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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 (represented as n=X) in category titles.

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	17
Cycle 1 Day 1; Pre-dose ; n=17	28.4 (115)
Cycle 1 Day 1; 30 Minutes Post-dose; n=1	201 (NA)
Cycle 1 Day 1; 1 Hour Post-dose; n=1	500 (NA)
Cycle 1 Day 1; 2 Hours Post-dose; n=1	733 (NA)
Cycle 1 Day 1; 4 Hours Post-dose; n=17	335 (233)
Cycle 1 Day 1; 8 Hours Post-dose; n= 1	353 (NA)
Cycle 1 Day 1; 96 Hours Post-dose; n=1	1400 (NA)
Cycle 1 Day 1; 168 Hours Post-dose; n=1	1440 (NA)
Cycle 2; Pre-dose; n=12	360 (383)
Cycle 2; 4 Hours Post-dose; n=13	959 (506)
Cycle 4; Pre-dose; n=9	600 (505)
Cycle 4; 4 Hours Post-dose; n=10	794 (597)
Cycle 8; Pre-dose; n=9	460 (543)
Cycle 8; 4 Hours Post-dose; n=7	727 (824)

26. Secondary Outcome

Title	Stage 1: Cohort 2: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab
Description	Blood samples were collected at indicated time points.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented as n=X) in category titles.

Arm/Group Title	Stage 1 (Cohort 2): Niraparib + Pembrolizumab
Arm/Group Description	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.
Measure Participants	21
Cycle 1 Day 1; Pre-dose ; n=19	NA (NA)
Cycle 1 Day 1; 30 Minutes Post-dose; n=3	24.5 (42.4)
Cycle 1 Day 1; 1 Hour Post-dose; n=3	189 (302)
Cycle 1 Day 1; 2 Hours Post-dose; n=3	264 (251)
Cycle 1 Day 1; 4 Hours Post-dose; n=21	345 (188)
Cycle 1 Day 1; 8 Hours Post-dose; n=2	238 (NA)
Cycle 1 Day 1; 24 Hours Post-dose; n=2	318 (NA)
Cycle 1 Day 1; 168 Hours Post-dose; n=1	759 (NA)
Cycle 1 Day 1; 336 Hours Post-dose; n=1	808 (NA)
Cycle 2; Pre-dose; n=12	767 (362)
Cycle 2; 4 Hours Post-dose; n=11	1170 (473)
Cycle 4; Pre-dose; n=9	805 (588)
Cycle 4; 30 Minutes Post-dose; n=1	841 (NA)
Cycle 4; 1 Hour Post-dose; n=1	1260 (NA)
Cycle 4; 2 Hours Post-dose; n=1	1290 (NA)
Cycle 4; 4 Hours Post-dose; n=8	1040 (668)
Cycle 4; 8 Hours, Post-dose; n=1	978 (NA)
Cycle 4; 24 Hours Post-dose; n=1	660 (NA)
Cycle 4; 96 Hours; n=1	773 (NA)
Cycle 4; 168 Hours; n=1	767 (NA)
Cycle 4; 336 Hours; n=1	924 (NA)
Cycle 8; Pre-dose; n=4	342 (123)
Cycle 8; 4 Hours post-dose; n=4	602 (290)

27. Secondary Outcome

Title	Stage 1: Cohort 3: Plasma Concentration of Niraparib Following Niraparib Monotherapy
Description	Blood samples were collected at indicated time points.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed (represented as n=X) in category titles.

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	3
Cycle 1 Day 1; Pre-dose ; n=1	NA (NA)
Cycle 1 Day 1; 4 Hours Post-dose; n=1	279 (NA)
Cycle 2; Pre-dose; n=2	469 (NA)
Cycle 2; 4 Hours Post-dose; n=2	717 (NA)
Cycle 4; Pre-dose ; n=1	615 (NA)
Cycle 4; 4 Hours Post-dose; n=1	871 (NA)
Cycle 8; Pre-dose ; n=1	478 (NA)
Cycle 8; 4 Hours Post-dose; n=1	913 (NA)

28. Secondary Outcome

Title	Stage 2: Cohorts 1A and 2A: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and TSR-042 (Dostarlimab)
Description	Blood samples were collected at indicated time points.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
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 (represented as n=X) in category titles.

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	12	0
Cycle 1 Day 1; Pre-dose ; n=12, 0	NA (NA)
Cycle 1 Day 1; 4 Hours Post-dose; n=12, 0	328 (254)
Cycle 2; Pre-dose; n=9, 0	669 (503)
Cycle 2; 4 Hours Post-dose; n=9, 0	967 (540)
Cycle 4; Pre-dose; n=8, 0	486 (243)
Cycle 4; 4 Hours Post-dose; n=8, 0	795 (228)
Cycle 9; Pre-dose; n=5, 0	456 (134)
Cycle 9; 4 Hours Post-dose; n=4, 0	766 (231)

29. Other Pre-specified Outcome

Title	Stage 1: Cohort 1: Overall Survival (OS)
Description	Overall survival
Time Frame	Up to a maximum of 29 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title

Stage 1 (Cohort 1): Niraparib + Pembrolizumab

Arm/Group Description

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.

Measure Participants

30. Other Pre-specified Outcome

Title	Stage 1: Cohort 2: Overall Survival
Description	Overall survival
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title

Stage 1 (Cohort 2): Niraparib + Pembrolizumab

Arm/Group Description

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.

Measure Participants

31. Other Pre-specified Outcome

Title	Stage 1: Cohort 3: Overall Survival
Description	Overall survival
Time Frame	Up to a maximum of 6 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Stage 1 (Cohort 3): Niraparib
Arm/Group Description	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.
Measure Participants	0

32. Other Pre-specified Outcome

Title	Stage 2: Cohorts 1A and 2A: Overall Survival
Description	Overall survival
Time Frame	Up to a maximum of 17 months

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)	Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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).	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).
Measure Participants	0	0

Adverse Events

	Stage 1 (Cohort 1): Niraparib + Pembrolizumab		Stage 1 (Cohort 2): Niraparib + Pembrolizumab		Stage 1 (Cohort 3): Niraparib		Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)		Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Time Frame	All-cause mortality, serious adverse events (SAE) and non-SAE were collected up to a maximum of 29 months in Cohort 1-Stage 1, up to a maximum of 17 months in Cohort 2-Stage 1, up to a maximum of 6 months in Cohort 3-Stage 1 and up to a maximum of 17 months in Cohort 1A-Stage 2.
Adverse Event Reporting Description	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 of study. The results presented are based on the Primary analysis up to a data cut-off date: 04-May-2020. Additional results will be provided after study completion.

Arm/Group Title	Stage 1 (Cohort 1): Niraparib + Pembrolizumab		Stage 1 (Cohort 2): Niraparib + Pembrolizumab		Stage 1 (Cohort 3): Niraparib		Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)		Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
Arm/Group Description	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.		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.		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.		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).		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).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/17 (47.1%)		15/21 (71.4%)		1/3 (33.3%)		4/12 (33.3%)		0/0 (NaN)
Serious Adverse Events
	Stage 1 (Cohort 1): Niraparib + Pembrolizumab		Stage 1 (Cohort 2): Niraparib + Pembrolizumab		Stage 1 (Cohort 3): Niraparib		Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)		Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/17 (64.7%)		14/21 (66.7%)		1/3 (33.3%)		7/12 (58.3%)		0/0 (NaN)
Blood and lymphatic system disorders
Anaemia	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Cardiac disorders
Atrial fibrillation	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Cardiac arrest	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pericardial effusion	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Gastrointestinal disorders
Diarrhoea	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Intestinal obstruction	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pancreatitis acute	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Proctalgia	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Small intestinal obstruction	0/17 (0%)		0/21 (0%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Constipation	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
General disorders
Chest pain	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Oedema peripheral	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Infections and infestations
Pneumonia	3/17 (17.6%)		3/21 (14.3%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Sepsis	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Catheter site abscess	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Diverticulitis	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Injury, poisoning and procedural complications
Fall	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Toxicity to various agents	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Investigations
Lipase increased	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Metabolism and nutrition disorders
Failure to thrive	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Lactic acidosis	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Neuroendocrine carcinoma of the skin	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Nervous system disorders
Encephalopathy	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Facial paralysis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Ischaemic stroke	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Syncope	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Psychiatric disorders
Mental status changes	2/17 (11.8%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Delirium	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Psychotic disorder	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Confusional state	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/17 (5.9%)		4/21 (19%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pleural effusion	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pulmonary embolism	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Haemoptysis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pneumonitis	0/17 (0%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Respiratory failure	0/17 (0%)		1/21 (4.8%)		1/3 (33.3%)		2/12 (16.7%)		0/0 (NaN)
Acute respiratory failure	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Vascular disorders
Hypotension	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Stage 1 (Cohort 1): Niraparib + Pembrolizumab		Stage 1 (Cohort 2): Niraparib + Pembrolizumab		Stage 1 (Cohort 3): Niraparib		Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab)		Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/17 (100%)		20/21 (95.2%)		3/3 (100%)		12/12 (100%)		0/0 (NaN)
Blood and lymphatic system disorders
Anaemia	5/17 (29.4%)		11/21 (52.4%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Thrombocytopenia	2/17 (11.8%)		0/21 (0%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Lymphadenitis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Thrombocytosis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Neutropenia	0/17 (0%)		0/21 (0%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Cardiac disorders
Atrial fibrillation	0/17 (0%)		3/21 (14.3%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Sinus tachycardia	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Tachycardia	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Atrial flutter	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Cardiac failure congestive	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Ear and labyrinth disorders
Tinnitus	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Vertigo	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Vertigo positional	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Endocrine disorders
Hypothyroidism	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Eye disorders
Vision blurred	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Gastrointestinal disorders
Nausea	7/17 (41.2%)		12/21 (57.1%)		2/3 (66.7%)		6/12 (50%)		0/0 (NaN)
Constipation	7/17 (41.2%)		10/21 (47.6%)		1/3 (33.3%)		5/12 (41.7%)		0/0 (NaN)
Diarrhoea	4/17 (23.5%)		4/21 (19%)		0/3 (0%)		6/12 (50%)		0/0 (NaN)
Vomiting	3/17 (17.6%)		5/21 (23.8%)		1/3 (33.3%)		3/12 (25%)		0/0 (NaN)
Stomatitis	1/17 (5.9%)		5/21 (23.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Abdominal pain	2/17 (11.8%)		1/21 (4.8%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Gastrooesophageal reflux disease	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Haematochezia	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Haemorrhoids	1/17 (5.9%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Colitis	2/17 (11.8%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Dysphagia	2/17 (11.8%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Haemorrhoidal haemorrhage	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Proctalgia	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Dyspepsia	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Levator syndrome	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Lip disorder	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pancreatic failure	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pancreatitis acute	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Small intestinal obstruction	0/17 (0%)		0/21 (0%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Abdominal pain upper	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
General disorders
Fatigue	8/17 (47.1%)		9/21 (42.9%)		1/3 (33.3%)		5/12 (41.7%)		0/0 (NaN)
Oedema peripheral	2/17 (11.8%)		5/21 (23.8%)		0/3 (0%)		4/12 (33.3%)		0/0 (NaN)
Chills	1/17 (5.9%)		3/21 (14.3%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Non-cardiac chest pain	2/17 (11.8%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Chest pain	0/17 (0%)		3/21 (14.3%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Gait disturbance	1/17 (5.9%)		2/21 (9.5%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Pain	0/17 (0%)		3/21 (14.3%)		1/3 (33.3%)		1/12 (8.3%)		0/0 (NaN)
Pyrexia	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Asthenia	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Malaise	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Catheter site irritation	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Catheter site pain	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Physical deconditioning	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Hepatobiliary disorders
Hepatobiliary disease	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Infections and infestations
Pneumonia	5/17 (29.4%)		3/21 (14.3%)		0/3 (0%)		4/12 (33.3%)		0/0 (NaN)
Upper respiratory tract infection	4/17 (23.5%)		3/21 (14.3%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Urinary tract infection	2/17 (11.8%)		2/21 (9.5%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Candida infection	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Sepsis	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Bacteraemia	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Catheter site abscess	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Fungal infection	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Mucosal infection	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Nasopharyngitis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Oral candidiasis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Sinusitis	1/17 (5.9%)		0/21 (0%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Viral infection	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Clostridium difficile colitis	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Injury, poisoning and procedural complications
Fall	2/17 (11.8%)		1/21 (4.8%)		1/3 (33.3%)		2/12 (16.7%)		0/0 (NaN)
Contusion	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Overdose	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Ankle fracture	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Arthropod sting	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Investigations
Platelet count decreased	2/17 (11.8%)		5/21 (23.8%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Weight decreased	2/17 (11.8%)		3/21 (14.3%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Blood alkaline phosphatase increased	1/17 (5.9%)		3/21 (14.3%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Aspartate aminotransferase increased	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Blood creatinine increased	1/17 (5.9%)		2/21 (9.5%)		1/3 (33.3%)		2/12 (16.7%)		0/0 (NaN)
Neutrophil count decreased	0/17 (0%)		3/21 (14.3%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Alanine aminotransferase increased	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Amylase increased	1/17 (5.9%)		1/21 (4.8%)		1/3 (33.3%)		1/12 (8.3%)		0/0 (NaN)
Hepatic enzyme increased	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Lymphocyte count decreased	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Blood magnesium decreased	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Glycosylated haemoglobin increased	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Haemoglobin decreased	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Vitamin D decreased	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Lipase increased	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Metabolism and nutrition disorders
Decreased appetite	7/17 (41.2%)		11/21 (52.4%)		1/3 (33.3%)		4/12 (33.3%)		0/0 (NaN)
Dehydration	2/17 (11.8%)		2/21 (9.5%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Hypokalaemia	2/17 (11.8%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Hyponatraemia	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Hypomagnesaemia	1/17 (5.9%)		1/21 (4.8%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Hypophosphataemia	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Lactic acidosis	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Failure to thrive	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Malnutrition	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Hyperglycaemia	0/17 (0%)		0/21 (0%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Hyperamylasaemia	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Hypercalcaemia	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Musculoskeletal and connective tissue disorders
Arthralgia	2/17 (11.8%)		4/21 (19%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Back pain	3/17 (17.6%)		3/21 (14.3%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Muscular weakness	1/17 (5.9%)		3/21 (14.3%)		0/3 (0%)		3/12 (25%)		0/0 (NaN)
Pain in extremity	3/17 (17.6%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Flank pain	2/17 (11.8%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Joint swelling	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Musculoskeletal pain	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Nervous system disorders
Dizziness	3/17 (17.6%)		1/21 (4.8%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Dysgeusia	1/17 (5.9%)		3/21 (14.3%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Peripheral sensory neuropathy	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Headache	1/17 (5.9%)		1/21 (4.8%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Lethargy	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Neuropathy peripheral	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Amnesia	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Cognitive disorder	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Dizziness postural	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Encephalopathy	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Facial paralysis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Horner's syndrome	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Ischaemic stroke	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Memory impairment	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Neuralgia	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Peroneal nerve palsy	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Syncope	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Aphasia	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Restless legs syndrome	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Taste disorder	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Psychiatric disorders
Insomnia	4/17 (23.5%)		4/21 (19%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Anxiety	4/17 (23.5%)		2/21 (9.5%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Confusional state	3/17 (17.6%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		1/0 (Infinity)
Depression	1/17 (5.9%)		2/21 (9.5%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Mental status changes	2/17 (11.8%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Agitation	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Delirium	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Psychotic disorder	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Renal and urinary disorders
Bladder spasm	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Dysuria	1/17 (5.9%)		0/21 (0%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Haematuria	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Incontinence	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Renal failure	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Urinary incontinence	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Urinary tract pain	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Pollakiuria	0/17 (0%)		0/21 (0%)		1/3 (33.3%)		1/12 (8.3%)		0/0 (NaN)
Acute kidney injury	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Calculus prostatic	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Penile pain	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Prostatic pain	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/17 (23.5%)		10/21 (47.6%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Cough	7/17 (41.2%)		3/21 (14.3%)		1/3 (33.3%)		1/12 (8.3%)		0/0 (NaN)
Nasal congestion	2/17 (11.8%)		1/21 (4.8%)		2/3 (66.7%)		1/12 (8.3%)		0/0 (NaN)
Pleural effusion	0/17 (0%)		3/21 (14.3%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Oropharyngeal pain	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Pneumonitis	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Productive cough	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Pulmonary embolism	1/17 (5.9%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Wheezing	0/17 (0%)		2/21 (9.5%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Haemoptysis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Hypoxia	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Rales	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Rhinorrhoea	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Tachypnoea	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Respiratory failure	0/17 (0%)		0/21 (0%)		1/3 (33.3%)		2/12 (16.7%)		0/0 (NaN)
Acute respiratory failure	0/17 (0%)		0/21 (0%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Skin and subcutaneous tissue disorders
Pruritus	3/17 (17.6%)		4/21 (19%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Rash maculo-papular	2/17 (11.8%)		2/21 (9.5%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Erythema	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Hyperhidrosis	1/17 (5.9%)		1/21 (4.8%)		1/3 (33.3%)		0/12 (0%)		0/0 (NaN)
Pain of skin	0/17 (0%)		2/21 (9.5%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Decubitus ulcer	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Dry skin	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Ecchymosis	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Rash	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		2/12 (16.7%)		0/0 (NaN)
Rash papular	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Skin hypopigmentation	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Alopecia	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Night sweats	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Skin ulcer	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Social circumstances
Immobile	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Surgical and medical procedures
Cholecystectomy	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Vascular disorders
Hypotension	2/17 (11.8%)		1/21 (4.8%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Haematoma	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		0/12 (0%)		0/0 (NaN)
Hypertension	1/17 (5.9%)		0/21 (0%)		0/3 (0%)		3/12 (25%)		0/0 (NaN)
Flushing	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)
Superior vena cava syndrome	0/17 (0%)		0/21 (0%)		0/3 (0%)		1/12 (8.3%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

Tesaro, Inc.

ClinicalTrials.gov Identifier:

NCT03308942

Other Study ID Numbers:

213352
3000-02-001

First Posted:

Oct 13, 2017

Last Update Posted:

Oct 21, 2021

Last Verified:

Sep 1, 2021

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

Study Details

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Primary Outcome Measures

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Other Outcome Measures

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Criteria

General Inclusion Criteria:

Cohort Specific Inclusion Criteria:

Exclusion Criteria for Cohorts 1, 1A , 2 and 2A:

Exclusion criteria for Cohort 3:

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Outcome Measure Data

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Adverse Events

All Cause Mortality

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