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
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
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Composite of pharmacokinetics of ASP8273 concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F
Composite of pharmacokinetics of midazolam concentration and its metabolites (plasma): Cmax, tmax, AUClast, AUCinf, t1/2, CL/F, and Vz/F
Best overall response rate
Disease control rate
Progression free survival