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

This study is composed of 2 parts: part 1 is the dose escalation phase and part 2 is the recommended Phase 2 dose (RP2D) phase, Food Effect (FE) cohort and Exon 20 cohort.

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