Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

PART A: Patients must have histologically or cytologically confirmed locally advanced (after failure of local therapy) or metastatic lung cancer (any histology, except carcinoid) stage IIIa, IIIb or IV

PART A: Existing formalin fixed paraffin embedded biopsy of the lung cancer with potentially sufficient material for analysis

PART A: Non-small cell lung cancer (NSCLC) with adenocarcinoma histology must have been previously tested for both epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements

PART A: Able (physically and financially) to travel to University of Colorado for clinical trial treatment

PART B: Patients must have histologically or cytologically confirmed locally advanced (after failure of local therapy) or metastatic lung cancer (any histology, except carcinoid) stage IIIa, IIIb or IV

PART B: Patients must be proven to meet marker criteria (FGFR1 silver in situ hybridization (SISH) + in situ hybridization (ISH) +, FGFR1 SISH+ ISH negative \[-ve\], FGFR1 SISH-ve ISH+, FGFR1 SISH-ve ISH-ve \[FGFR1 double negative cohort\] or ret proto-oncogene \[RET\] FISH+) prior to enrollment into Part B (treatment); adenocarcinoma patients must be known to not possess either an EGFR mutation or an ALK rearrangement in their tumor (if positive for one, testing for both is not required)

PART B: Patients must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

PART B: Patients may have received any number of lines of prior therapy

PART B: Life expectancy of \>= 3 months

PART B: Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

PART B: Leukocytes \>= 3,000/mcL

PART B: Absolute neutrophil count \>= 1,500/mcL

PART B: Hemoglobin \>= 9 g/dL

PART B: Platelets \>= 100,000/mcL

PART B: Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), unless due to Gilbert's syndrome

PART B: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN

PART B: Creatinine =\< 1.5 X ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal

PART B: Serum lipase =\< 1.5 X ULN

PART B: Serum amylase =\< 1.5 X ULN

PART B: Previous treatment related side-effects/adverse events must have resolved to at least grade 1 or, at the discretion of the investigator, select stable grade 2 toxicities (e.g. alopecia or fatigue) may be permissible if unchanging in grade for at least 3 months following discussion with the principal investigator (PI)

PART B: Patients with central nervous system (CNS) metastases are eligible for enrollment if they have no overt evidence of neurological deficits, and are not requiring anti-epileptics or steroids to control their neurological symptoms; patients with known CNS metastases must have relevant CNS imaging performed approximately coincident with body imaging during response assessments

PART B: The effects of ponatinib on the developing human fetus are unknown; for this reason women of child-bearing potential must have a negative urine or blood pregnancy test at screening for Part B; women of child-bearing potential and men must also have documented agreement to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of screening until 30 days after the end of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, they should inform the treating physician immediately

PART B: Ability to understand and the willingness to sign a written informed consent document

What this study is about