Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer

This research study is studying a combination of drugs as a possible treatment for EGFR-Mutated Advanced Lung Cancer. The names of the study drugs involved in this study are Niraparib and Osimertinib.

Inclusion Criteria: * Participants must have histologically or cytologically confirmed stage IV (AJCC 8th ed.) NSCLC with an activating EGFR mutation as identified in a CLIA-approved laboratory. * Presence of evaluable disease, either measure or non-measurable, in accordance with RECIST 1.1 criteria. * Participants must have had clinical progression on osimertinib at any prior time, i.e., intervening therapy between osimertinib and study enrollment is allowed. * Participants must have access to commercial osimertinib. * Participants must not have received any prior PARP inhibitor therapy. * Age minimum 18 years. * ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A). * Life expectancy of greater than 6 months. * Participants must have normal organ and marrow function as defined below: * absolute neutrophil count ≥1,500/mcL * platelets ≥100,000/mcL * hemoglobin ≥ 9 g/dL * bilirubin total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤2.0 in patients with known Gilberts syndrome or liver metastases) OR direct bilirubin ≤ 1 x ULN * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, unless liver metastases are present, in which case they must be ≤ 5 x ULN * creatinine ≤ 1.5 x institutional ULN OR * creatinine clearance ≥50 mL/min using the Cockcroft-Gault equation * Participants must have undergone a prior tumor biopsy upon clinical progression on osimertinib. If it was not feasible or medically safe to undergo a biopsy a patient may enroll with permission of the PI. * The effects of Niraparib on the developing human fetus are unknown but based on its mechanism of action Niraparib may cause fetal harm when administered to a pregnant woman. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry through 180 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Niraparib administration. * Female participant must have a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons): --≥ 45 years of age and has not had menses for \>1 year * Patients who have been amenorrhoeic for \