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

Exclusion Criteria

• •Participants must not be simultaneously enrolled in any interventional clinical trial.
• •Participants receiving any systemic standard of care or investigational therapy within 4 weeks from the last dose prior to planned study treatment, with the exception of osimertinib. This time frame may be shortened for participants depending on the characteristics of the individual therapy, after discussion with the Study PI. For investigational therapy, the time frame will not be shortened to less than at least 5 half-lives of the investigational agent.
• •Patients receiving radiation therapy encompassing \> 20% of the bone marrow by investigator's estimate within 14 days, or any radiation therapy within 7 days from the last treatment prior to planned study treatment. However, small volume palliative radiation therapy with no or little bone marrow exposure is allowed at the investigator's discretion.
• •Participants may receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
• •Participants who had any major surgery within the past 3 weeks (excluding vascular access placement, mediastinoscopy, or biopsies performed by an interventional service) and participant must have recovered from any surgical effects.
• •Participants with symptomatic uncontrolled brain or leptomeningeal metastases. Participants with brain metastases that have been treated with prior radiation therapy and are stable on a subsequent scan are allowed. Participants with untreated possible brain metastases that are ≤ 1 cm and asymptomatic are allowed.
• •Participants who received a transfusion (platelets, red blood cells) or hematopoetic growth factors within 4 weeks of study treatment.
• •Presence of any of the following cardiac criteria/factors:
• •Resting QT interval of \>470 msec.
• •Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, such as complete left bundle branch block, third degree heart block, or second degree heart block.
• •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval.
• •Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required corticosteroid treatment, or any evidence of clinically active interstitial lung disease.
• •Participants with known hypersensitivity to the components or excipients of niraparib or osimertinib.
• •Participants may not have received prior treatment with anti-PD1, -PDL1, or -CTLA4 inhibitors.
• •Participants with a second, clinically active, malignancy. Participants must not have known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or psychiatric illness/social situations that would limit compliance with study requirements.
• •Participants must not have had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• •Participants must not have current evidence of any condition, therapy, or laboratory abnormality (including active or uncontrolled myelosuppression \[ie, anemia, leukopenia, neutropenia, thrombocytopenia\]) that might confound the results of the study or interfere with the patient's participation for the full duration of the study treatment or that makes it not in the best interest of the patient to participate in the opinion of the investigator or sponsor.
• •Patients must not have known, active hepatitis B/C.
• •Known disorder affecting gastrointestinal absorption.
• •Patients must not be pregnant or breastfeeding, or expecting to conceive children, within the projected duration of the study treatment, or for 180 days after the last dose of study treatment.
• •Known HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with Niraparib. In addition, these participants may be at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated, However, HIV testing is not required.