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

• ClinicalTrials.gov Identifier: NCT03308942
• Recruitment Status: Completed
• First Posted: October 13, 2017
• Results First Posted: July 7, 2021
• Last Update Posted: October 21, 2021
• Sponsor: Tesaro, Inc.
• Information provided by (Responsible Party): Tesaro, Inc.

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 (Clinical Trial)
• 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.
• 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: September 29, 2017
• Actual Primary Completion Date: May 4, 2020
• Actual Study Completion Date: August 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 :

1. Stage 1: Cohort 1: Objective Response Rate (ORR) [ Time Frame: Up to a maximum of 29 months ]
   ORR is the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Data has been presented for participants with NSCLC whose tumors have high PD-L1 expression (TPS>=50%). Confidence interval was calculated using binomial exact method.
2. Stage 1: Cohort 2: Objective Response Rate [ Time Frame: Up to a maximum of 17 months ]
   ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Data has been presented for participants with NSCLC having PD-L1 expression in tumors (TPS: 1 to 49%). Confidence interval was calculated using binomial exact method.
3. Stage 1: Cohort 3: Objective Response Rate [ Time Frame: Up to a maximum of 6 months ]
   ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Data is presented for participants with locally advanced and metastatic squamous NSCLC. Confidence interval was calculated using binomial exact method.
4. Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate [ Time Frame: Up to a maximum of 17 months ]
   ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Confidence interval was calculated using binomial exact method.

Secondary Outcome Measures :

1. Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [ Time Frame: 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.
2. Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs [ Time Frame: 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.
3. Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs [ Time Frame: 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.
4. Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs [ Time Frame: 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.
5. Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs [ Time Frame: 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.
6. Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs [ Time Frame: 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.
7. Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs [ Time Frame: 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.
8. Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs [ Time Frame: 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.
9. Stage 1: Cohort 1: Duration of Response [ Time Frame: 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.
10. Stage 1: Cohort 2: Duration of Response [ Time Frame: 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.
11. Stage 1 : Cohort 3: Duration of Response [ Time Frame: 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.
12. Stage 2: Cohorts 1A and 2A: Duration of Response [ Time Frame: 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.
13. Stage 1 : Cohort 1: Disease Control Rate [ Time Frame: 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.
14. Stage 1 : Cohort 2: Disease Control Rate [ Time Frame: 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.
15. Stage 1 : Cohort 3: Disease Control Rate [ Time Frame: 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.
16. Stage 2: Cohorts 1A and 2A: Disease Control Rate [ Time Frame: 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.
17. Stage 1 : Cohort 1: Progression-free Survival [ Time Frame: 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.
18. Stage 1 : Cohort 2: Progression-free Survival [ Time Frame: 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.
19. Stage 1 : Cohort 3: Progression-free Survival [ Time Frame: 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.
20. Stage 2: Cohorts 1A and 2A: Progression-free Survival [ Time Frame: 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.
21. Stage 1: Cohort 1: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab [ 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) ]
    Blood samples were collected at indicated time points.
22. Stage 1: Cohort 2: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab [ 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) ]
    Blood samples were collected at indicated time points.
23. Stage 1: Cohort 3: Plasma Concentration of Niraparib Following Niraparib Monotherapy [ 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) ]
    Blood samples were collected at indicated time points.
24. Stage 2: Cohorts 1A and 2A: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and TSR-042 (Dostarlimab) [ 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) ]
    Blood samples were collected at indicated time points.

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

  1. Absolute neutrophil count (ANC) >= 1500 per microliter (/µL).
  2. Platelets >= 100,000/µL.
  3. Hemoglobin >= 9 grams per deciliter (g/dL) or >= 5.6 millimoles per liter (mmol/L).
  4. 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.
  5. 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.
  6. 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:

  a) 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.

iii) 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

United States, California

GSK Investigational Site

Whittier, California, United States, 90603

United States, Florida

GSK Investigational Site

Port Saint Lucie, Florida, United States, 34952

United States, Georgia

GSK Investigational Site

Atlanta, Georgia, United States, 30322

United States, Illinois

GSK Investigational Site

Harvey, Illinois, United States, 60426

GSK Investigational Site

Tinley Park, Illinois, United States, 60487

United States, Massachusetts

GSK Investigational Site

Boston, Massachusetts, United States, 02215

United States, New Jersey

GSK Investigational Site

Morristown, New Jersey, United States, 07962-1956

United States, New York

GSK Investigational Site

Buffalo, New York, United States, 14263

United States, North Carolina

GSK Investigational Site

Durham, North Carolina, United States, 27710

United States, Ohio

GSK Investigational Site

Canton, Ohio, United States, 44718

GSK Investigational Site

Cleveland, Ohio, United States, 44106

GSK Investigational Site

Columbus, Ohio, United States, 31904

GSK Investigational Site

Toledo, Ohio, United States, 43623

United States, Tennessee

GSK Investigational Site

Nashville, Tennessee, United States, 37203

United States, Washington

GSK Investigational Site

Kennewick, Washington, United States, 99336

GSK Investigational Site

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Tesaro, Inc.

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by Tesaro, Inc.:

Study Protocol  [PDF] February 12, 2021

Statistical Analysis Plan  [PDF] June 8, 2020

More Information

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT03308942
• Other Study ID Numbers: 213352; 3000-02-001 ( Other Identifier: Tesaro )
• First Posted: October 13, 2017
• Results First Posted: July 7, 2021
• Last Update Posted: October 21, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tesaro, Inc.:

Niraparib; NSCLC; Pembrolizumab; Dostarlimab; TSR-042

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pembrolizumab; Niraparib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action