A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations

Inclusion Criteria: * Non-child bearing potential or able to follow birth control requirements * Eastern Cooperative Oncology Group (ECOG) ≤ 1 * Life expectancy ≥ 12 weeks * Laboratory criteria as: * Neutrophil count ≥ 1,500/mm3 * Platelet count ≥ 7.5 x 104 /mm3 * Hemoglobin ≥ 9.0 g/dL * Lymphocyte count ≥ 500/mm3 * Serum creatinine \< 1.5 x institutional Upper Limit of Normal (ULN) or an estimated glomerular filtration rate (eGFR) of \> 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation * Total bilirubin \< 1.5 x ULN (except for subjects with documented Gilbert's syndrome) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 x ULN * Dose escalation subjects: Epidermal Growth Factor Receptor (EGFR) activating mutation by local testing: exon 18 G719X, exon 19 deletion, exon 21 L861Q, exon 21 L858R or exon 20 insertion; and received prior treatment with EGFR Tyrosine Kinase Inhibitor (TKI) * Response expansion/RP2D expansion/ FE Cohort subjects: disease progression on or was intolerant to prior EGFR TKI; activating mutation as above AND T790M mutation; tumor sample subsequent to EGFR TKI is available for central testing; at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Inclusion Criteria for Exon 20 cohort: * Subject on any line of treatment and has an EGFR exon 20 insertion mutation on examination of an NSCLC tissue or cellular specimen. Local testing may determine eligibility and a tumor sample should also be sent for central testing. * Subjects must have at least 1 measurable lesion based on RECIST version 1.1. Exclusion Criteria: * Any ongoing toxicity ≥ Grade 2 attributable to prior Non-Small-Cell Lung Cancer (NSCLC) treatment * Prior EGFR inhibitor within 6 days; received prior treatment with any other agent with antitumor activity chemotherapy, radiotherapy, or immunotherapy within 14 days; any investigational therapy within 28 days or 5 half-lives, whichever is shorter; blood transfusion or hemopoietic factor within 14 days; major surgery within 14 days; any strong CYP3A4 inhibitors within 7 days * Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) or Human Immunodeficiency Virus (HIV) * Symptomatic Central Nervous System (CNS) metastasis * Active infection requiring systemic therapy within 14 days * Severe or uncontrolled systemic diseases including uncontrolled hypertension * History of or active interstitial lung disease * Screening QTcF \>450 msec or current medication known to prolong QT * ≥ Grade 2 cardiac arrhythmia or uncontrolled atrial fib of any grade; Class 3 or 4 New York Heart Association congestive heart failure; history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months * History of gastrointestinal ulcer or bleeding within 3 months; any digestive tract dysfunction * Concurrent corneal disorder or ophthalmologic condition making subject unsuitable * RP2D cohort subjects: contraindications to midazolam, any other midazolam within 7 days, or any medications or supplements known to be strong CYP3A inhibitors within 7 days or inducers within 12 days * Any other malignancy requiring treatment