Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer

Inclusion Criteria: * Age \>= 18 years. Children are excluded from this study because neither dosing nor safety data are currently available for AZD9291 or BC2059 in patients \< 18 years of age * Pathology-confirmed metastatic NSCLC * A common activating mutation must be present in the EGFR gene, i.e., exon 19 deletion or L858R. The presence of uncommon EGFR mutations, e.g., G719X, S768I, or L861Q are also permitted if they co-occur with a common activating mutation. Mutation status must be determined using a tumor biopsy by local Clinical Laboratory Improvement Act (CLIA)-certified assessment. Mutations identified by blood-based testing can be provided, but must be verified by tumor biopsy * The presence of a concurrent T790M mutation, while uncommon in patients who are naïve to treatment with EGFR TKIs, is also permitted * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * The patient must be able to swallow pills * Life expectancy \> 3 months * Leukocytes \>= 3,000/mcL * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Hemoglobin \>= 90 g/L * Total bilirubin =\< 1.5 x institutional upper limit normal (ULN) and up to 3 mg/dL for patients with Gilbert's * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase ALT (serum glutamate pyruvate transaminase \[S…