Trial Information

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 who have documented somatic HER2 mutations and
who have received at least one prior cytotoxic chemotherapy regimen. Patients will be
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 the neratinib monotherapy
arm will be given the option to add temsirolimus 8 mg IV once weekly.

All patients on combination therapy may be dose-escalated with respect to temsirolimus dose
to 15 mg/week at the end of first cycle of treatment with the combination, if well tolerated
and at the physician's discretion. In the event that the neratinib 240 mg/day plus
temsirolimus 15 mg/week dose is not well tolerated, the patient will be subsequently dose
reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week.

Dosing will be continuous on nominal 3-week cycles until evidence of progressive disease,
unacceptable toxicity, or patient withdrawal of consent.

All eligible patients enrolled will have their disease measured radiographically at
baseline. Patients will undergo radiographic evaluation of their disease every 6 weeks until
disease progression or withdrawal from the study.