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

Inclusion Criteria

• Aged ≥18 years at the time of signing the informed consent.
• Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage IV).
• Documented somatic ErbB2 (HER2) activating mutation.
• Patients with anaplastic lymphoma kinase (ALK) translocations must have received crizotinib, except for cases of intolerable toxicity to crizotinib.
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) status 12.5 mg/day or dexamethasone >2 mg/day, excluding inhaled steroids).
• Currently breast feeding.
• Symptomatic or unstable brain metastases.
• QTc interval >0.450 seconds for men and >0.470 seconds for women, or known history of QTc prolongation or Torsades de Pointes (TdP).
• 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).
• Prior exposure to neratinib or mTOR inhibitor.
• Active infection or unexplained fever >38.5°C (101.3°F).
• Unable or unwilling to swallow tablets.
• 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.
• Known hypersensitivity to any component of the investigational products.
• Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin [HbA1c] >6.5%).
• Screening laboratory assessments outside the following limits: ANC 1.5 x institutional upper limit of normal (ULN), AST and/or ALT 5 minutes, Creatinine clearance <50 mL/min.