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

Exclusion Criteria

• •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).
• •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.