Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial)

Patients must be assigned to S1900C. Assignment to S1900C is determined by the LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker eligibility for S1900C is based on the identification of a pathogenic somatic mutation in STK11 or STK11 bi-allelic loss on tumor

Patients who received prior adjuvant platinum-based therapy post-surgical resection for stage I-III disease (i.e. the patient has not received platinum-based chemotherapy for Stage IV or recurrent disease) must have had disease progression during or after platinum-based chemotherapy that occurred less than (\<) 365 days from the last date that the patient received that therapy

Patients must be able to swallow capsules whole

Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g., veliparib, olaparib, rucaparib, niraparib, talazoparib) as its primary pharmacology

Patients must not be taking, nor plan to take while on protocol treatment strong P-glycoprotein (P-gp) inhibitors (e.g. dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), P-gp inducers (rifampin, ritonavir, tipranavir), or strong breast cancer resistance protein (BCRP) inhibitors (e.g. elacridar)

Patients must have progressed following their most recent line of therapy

Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration. Patients must have recovered (=\< grade 1) from any side effects of prior therapy. Patients must not have received any radiation therapy within 14 days prior to sub-study registration

Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable

Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to sub-study registration. CT and MRI scans must be submitted for central review via Transfer of Images and Data (TRIAD)

Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to sub-study registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration

Patient must not have had a major surgery within 14 days prior to sub-study registration. Patient must have fully recovered from the effects of prior surgery in the opinion of the treating investigator

Serum bilirubin =\< institutional upper limit of normal (IULN) (within 28 days prior to sub-study registration). For patients with liver metastases, bilirubin must be =\< 5 x IULN

Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =\< 2 x IULN within 28 days prior to sub-study registration (if both ALT and AST are done, both must be =\< 2 IULN). For patients with liver metastases, either ALT or AST must be =\< 5 x IULN (if both ALT and AST are done, both must be =\< 5 x IULN)

Patients must have a serum creatinine =\< the IULN or calculated creatinine clearance \>= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to sub-study registration

Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration

Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia

Pre-study history and physical exam must be obtained within 28 days prior to sub-study registration

No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

Absolute neutrophil count (ANC) \>= 1,500/mcl (obtained within 28 days prior to sub-study registration). Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to sub-study registration)

Platelet count \>= 100,000 mcl (obtained within 28 days prior to sub-study registration). Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to sub-study registration)

Hemoglobin \>= 9 g/dL (obtained within 28 days prior to sub-study registration). Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to sub-study registration)

Patients must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)

Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens

What this study is about