Crossover Study to Assess the Relative Bioavailability of Niraparib Tablet Compared to Niraparib Capsule

Main criteria for inclusion:

PK Phase:

To be considered eligible to participate in this study, all of the following requirements
must be met:

- Patients with histologically or cytologically confirmed diagnosis of metastatic or
locally advanced solid tumors that have failed to respond to standard therapy, has
progressed despite standard therapy, or for which no standard therapy exists, and who
may benefit from treatment with a PARP inhibitor as assessed by the Investigator.

- ECOG performance status of 0 to 2.

- Adequate organ function as defined below:

- Absolute neutrophil count ≥ 1,500/μL

- Platelets ≥ 100,000/μL

- Hemoglobin ≥ 9 g/dL (5.6 mM)

- Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) or a calculated
creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation or 24-hour
urine creatinine clearance.

- 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.

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

- Patient has 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).

- Female Patient 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 Screening through 180 days after the
last dose of study drug,

- Male patient agrees to use an adequate method of contraception and not donate sperm
starting with the first dose of study drug through 90 days after the last dose of
study drug

Key Exclusion, PK Phase:

- Known diagnosis of immunodeficiency

- Symptomatic uncontrolled brain or leptomeningeal metastases.

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

- Patient is considered a poor medical risk due to a serious, uncontrolled medical
disorder; nonmalignant systemic disease; or active, uncontrolled infection.

- Known history of myelodysplastic syndrome or acute myeloid leukemia.

- Patient is currently receiving a sensitive cytochrome P450 (CYP) 1A2 substrates with a
narrow therapeutic index (e.g., tizanidine and theophylline) (Does not apply for
Extension Phase).

- Patient is currently taking any of the following P-glycoprotein (P-gp) inhibitors:
amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan,
cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole,
ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor,
and verapamil (Does not apply for Extension Phase).

- Patient taking proton pump inhibitors, antacids, or histamine 2 blockers within 48
hours prior to study drug administration, and/or within 6 hours after study drug
administration (Does not apply for Extension Phase).

- Patient has gastric, gastro-esophageal or esophageal cancer; patient is unable to
swallow orally administered medication; or patient has gastrointestinal disorders or
significant gastrointestinal resection likely to interfere with the absorption of
niraparib.

- Patient has known active hepatic disease

- Patient has a past or current history of chronic alcohol use.

- Patient has significant pleural effusion or ascites that is expected to require
drainage during the PK Phase (Does not apply for Extension Phase).

Key Inclusion, Extension Phase:

- ECOG performance status of 0 to 2.

- Adequate organ function as defined below

- Absolute neutrophil count ≥ 1,500/μL

- Platelets ≥ 100,000/μL

- Hemoglobin ≥ 9 g/dL (5.6 mM)

- Serum creatinine ≤ 1.5 × the ULN or a calculated creatinine clearance ≥ 60 mL/min
using the Cockcroft-Gault equation or 24-hour urine creatinine clearance

- 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.

- AST and ALT ≤ 2.5 × ULN unless liver metastases are present, in which case, they
must be ≤5 × ULN

- Female patient 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 Screening through 180 days after the
last dose of study drug.

- Male patient agrees to use an adequate method of contraception and not donate sperm
starting with the first dose of study drug through 90 days after the last dose of
study drug.