A Phase 2 Study of Osimertinib and S-1 in Treatment Resistant EGFR Mutant NSCLC

Inclusion Criteria: * Patients must have histologically or cytologically confirmed EGFR mutant NSCLC. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan, MRI, or calipers by clinical exam. * Prior therapy: Patient with recurrent and/or metastatic EGFR mutant NSCLC, that has progressed on osimertinib as most recent line of treatment, and the primary doctor intends to continue with osimertinib treatment. * Patients with no matched alterations (tumor or plasma) where clinical trials or approved systemic anti-cancer therapy are available, are eligible * Patients with matched alterations on rebiopsy (tumor or plasma) who declined matching clinical trials, or approved systemic anti-cancer therapy, are eligible * Age ≥21 years. * ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A). * Patients must have adequate organ and marrow function as defined below: * absolute neutrophil count ≥1,500/mcL * platelets ≥100,000/mcL * total bilirubin ≤ institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN * creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral loa…