Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer

General Inclusion Criteria:

1. Male or female at least 18 years of age

2. 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

3. Measurable disease by RECIST v1.1

4. ECOG performance status of 0 to 1

5. Adequate organ function, defined as (Note: CBC test should be obtained without
transfusion or receipt of colony stimulating factors within 2 weeks before obtaining
sample):

1. Absolute neutrophil count (ANC) ≥ 1500/µL

2. Platelets ≥ 100,000/µL

3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L

4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine
clearance ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine
levels > 1.5× institutional ULN

5. Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients
with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct
bilirubin.

6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
unless liver metastases are present, in which case they must be ≤ 5× ULN

6. Patient must have recovered to Grade 1 toxicity from prior cancer therapy (a patient
with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may
qualify for this study).

7. Provision of (archival or fresh) FFPE tumor tissue.

8. Able to take oral medications

9. Female patient has a negative serum pregnancy test within 72 hours prior to taking
study drug if of childbearing potential, and agrees to abstain from activities that
could result in pregnancy from enrollment through 120 days after the last dose of
study treatment, or be of non-childbearing potential.

10. Male patient agrees to use an adequate method of contraception starting with the first
dose of study therapy through 120 days after the last dose of study therapy.

11. Able to understand the study procedures and agree to participate in the study by
providing written informed consent

Cohort Specific Inclusion Criteria:

1. Cohorts 1 and 1A (combination of niraparib and PD-1 inhibitor): patients must have
tumors with high PD-L1 expression (TPS ≥ 50%) per local assessment; with no known
EGFR-sensitizing mutation and/or ROS-1 or ALK translocations, and no prior systemic
chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC

2. Cohorts 2 and 2A (combination of niraparib and PD-1 inhibitor): patients 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

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

1. 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

2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

3. Known hypersensitivity to the components of niraparib, PD-1 inhibitor, or their
excipients

4. Known EGFR (exon 19 and 21) mutations, ALK translocations, and/or ROS-1 translocations

5. Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or
laboratory abnormality that might confound the study results, or interfere with the
patient's participation for the full duration of the study treatment.

6. Known diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of study
treatment

7. Immunocompromised patient (Note: patients with splenectomy are allowed)

8. 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

9. Symptomatic uncontrolled brain or leptomeningeal metastases

10. Active autoimmune disease that required systemic treatment in the past 2 years (ie,
with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
systemic treatment

11. Major surgery within 3 weeks of starting the study or patient has not recovered from
any effects of any major surgery

12. Other active concomitant malignancy that warrants systemic therapy

13. 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, or any psychiatric disorder
that prohibits obtaining informed consent

14. Known interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis
requiring steroid treatment

15. Patient 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

16. Male patient is expecting to donate sperm or father children while receiving study
drug or for 120 days after the last dose of study treatment

17. Known active hepatic disease (known hepatic cirrhosis, hepatitis B surface antigen
positive status, or suspected active hepatitis C infection)

18. Prior treatment with a known poly (ADP-ribose) polymerase (PARP) inhibitor

19. Patient who received a live vaccine within 30 days of planned start of study therapy

20. Known history of MDS or AML