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.
Patients will be randomized at study entry into 1 of 2 treatment arms:
investigational Product, Dose, and administration:
* arm a: neratinib monotherapy dosing: Six 40 mg tablets (total daily dose 240 mg) orally, once daily with
food, preferably in the morning, continuously in 21-day cycles.
* arm B: neratinib plus temsirolimus dosing: Six neratinib 40 mg tablets (total daily dose 240 mg) orally,
once daily with food, preferably in the morning, continuously in 21-day cycles, plus temsirolimus 8 mg
weekly by iV infusion.
* neratinib plus temsirolimus dose escalation: Six neratinib 40 mg tablets (total daily dose 240 mg) orally,
once daily with food, preferably in the morning, continuously in 21-day cycles, plus temsirolimus 15 mg
weekly by iV infusion
The data for patients in this study is regularly evaluated by the PuMa-neR-4201 Data Review Committee (DRC). Response and safety data for 27 patients (13 in arm a and 14 in arm B) enrolled into the Stage 1 portion of this study were reviewed by the DRC on 13 May 2014. The data indicated that arm a (neratinib monotherapy) did not meet the minimum of 2 responses at 12 weeks required for arm a expansion. The data also showed that arm B (neratinib + temsirolimus) has met the minimum 2/13 responses. Safety data were comparable between the two arms. Per Stage 2 of the study design, enrollment into arm a will be discontinued and enrollment into arm B has been expanded with a goal to reach a target of 39 patients total into that arm effective 15 MaY 2014.
Each patient will be entered into this study only if she/he meets all of the following criteria:
1. Aged >=18 years at the time of signing the informed consent.
2. Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage
3. Documented somatic ErbB2 (HER2) activating mutation.
4. Patients with anaplastic lymphoma kinase (ALK) translocations must have received
crizotinib, except for cases of intolerable toxicity to crizotinib
5. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).
6. Eastern Cooperative Oncology Group (ECOG) status <=2.
7. Left ventricular ejection fraction (LVEF) >=50% measured by multiple-gated acquisition scan
(MUGA) or echocardiogram (ECHO).
8. Negative [BETA]-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women
of reproductive capacity (those who are biologically capable of having children) and for
women less than 12 months after menopause.
9. Men and women of childbearing potential must agree and commit to the use of a highly
effective method of contraception, as determined to be acceptable by the Investigator, from
the time of informed consent until 3 months after the last dose of the investigational products.
10. Provide written, informed consent to participate in the study and follow the study procedures.