A Phase Ib Study of AZD9291 (Osimertinib) and BC2059 (Tegavivint) As First-Line Therapy in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)
This phase Ib trial is to find out the best dose, possible benefits and/or side effects of osimertinib and tegavivint as first-line therapy in treating patients with EGFR-mutant non-small cell lung cancer that has spread to other places in the body (metastatic). Osimertinib and tegavivint may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
• 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 \[SGPT\]) =\< 2.5 x institutional ULN and =\< 5 x institutional ULN for patients with liver metastases
• Creatinine within 1.5 x ULN OR glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2 (measured or calculated by Cockcroft and Gault equation) -confirmation of creatinine clearance is only required for patients with creatinine levels above institutional upper limit of normal
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
• If history of hepatitis C virus (HCV) infection, it must be treated and have an undetectable viral load
• Patients with treated brain metastases are asymptomatic and not requiring ongoing treatment
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS)-specific treatment is not required and is unlikely to be required during the first cycle of therapy. Clinical stability on a stable dose of decadron is permitted
• Patients with a prior or concurrent malignancy whose natural history or treatment will not interfere with the safety or efficacy assessment of the investigational drugs are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
• Ability to understand and sign a written informed consent document