A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients With Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations

This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with NSCLC and documented somatic HER2 mutations. Patients randomized at study entry into 1 of 2 treatment arms: Arm A: neratinib 240 mg orally once daily Arm B: neratinib 240 mg orally once daily plus temsirolimus 8 mg once weekly by intravenous (IV) infusion In the case of disease progression, patients initially assigned to neratinib monotherapy arm given option to add temsirolimus 8 mg IV once weekly. Patients on combination therapy given option to dose-escalate temsirolimus to 15 mg/week at the end of first cycle of treatment, if well tolerated and at the physician's discretion. If neratinib 240 mg/day plus temsirolimus 15 mg/week dose not well tolerated, patient subsequently dose reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week. Dosing continuous on nominal 3-week cycles until evidence of progressive disease, unacceptable toxicity, or patient withdrawal of consent. Disease measured radiographically at baseline and every 6 weeks until disease progression or withdrawal from the study.