Dasatinib and Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer With EGFR Mutations

Exclusion Criteria

• •Patients must have adequate archival material from a previous biopsy to determine EGFR mutation status and Cripto-1 expression, or undergo a biopsy of fresh tissue of the primary cancer or a metastatic site in order to make these determinations, if archival material is not available.
• •Presence of sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q). Patients with the T790M mutation will also be eligible.
• •No prior treatment with an EGFR TKI for the advanced NSCLC.
• •ECOG performance status of 0-2.
• •Patients must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. See Section 7.1.2 for the evaluation of measurable disease.
• •Prior systemic treatment is allowed, but toxicities of prior therapy must be resolved to grade 1 or less as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
• •Adequate organ and bone marrow function (hemoglobin \> 9 g/dL; absolute neutrophil count \> 1.5 x 109/L; platelet counts \> 100 x 109/L; serum bilirubin \< 2 x ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN or \< 5 x ULN if liver metastases; calculated creatinine clearance \> 50 mL/min).
• •No uncontrolled arrhythmia; no myocardial infarction in the last 6 months.
• •Life expectancy of at least 12 weeks.
• •Age \> 18 years.
• •Ability to understand and willingness to sign a written informed consent document.
• •Patients who have had radiotherapy (except for palliative reasons), immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas or mitomycin) before treatment, or those who have ongoing toxic manifestations of previous treatments, with the exception of alopecia, of grade higher than 1.
• •Major thoracic or abdominal surgery from which the patient has not sufficiently recovered yet.
• •Untreated and uncontrolled second tumor in the past 2 years.
• •Logistical or psychological hindrance to participation in clinical research.