Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer

Exclusion Criteria

• •1. Previous treatment with any investigational agent ≤14 days prior to the initiation of investigational products.
• •2. Previous treatment with any strong inhibitor and/or inducer of CYP3A4 enzyme or sensitive P-glycoprotein (P-gp) substrates ≤30 days prior to the initiation of investigational products.
• •3. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
• •4. Major surgery \<30 days of starting treatment.
• •5. Chronic steroid use (prednisone \>12.5 mg/day or dexamethasone \>2 mg/day, excluding inhaled steroids).
• •6. Currently breast feeding.
• •7. Symptomatic or unstable brain metastases.
• •8. QTc interval \>0.450 seconds for men and \>0.470 seconds for women, or known history of QTc prolongation or Torsades de Pointes (TdP).
• •9. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 4.0 \[CTCAE v.4.0\] diarrhea of any etiology at baseline).
• •10. Prior exposure to neratinib or mTOR inhibitor.
• •11. Active infection or unexplained fever \>38.5°C (101.3°F).
• •12. Unable or unwilling to swallow tablets.
• •13. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
• •14. Known hypersensitivity to any component of the investigational products.
• •15. Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin \[HbA1c\] \>6.5%).
• •16. Screening laboratory assessments outside the following limits: ANC \<1000/μL (\<1.0 x 109/L), Platelet count \<75,000/μL (\<75 x 109/L), Hemoglobin \<8 g/dL, transfusions allowed, must be at least 7 days prior to baseline, Total bilirubin \>1.5 x institutional upper limit of normal (ULN), AST and/or ALT 5 minutes, Creatinine clearance \<50 mL/min.