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

Phase 2
18 Years
Open (Enrolling)
HER2-mutant Non-Small Cell Lung Cancer

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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.

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.

Exclusion Criteria:

- Previous treatment with any investigational agent ≤30 days prior to the initiation of
investigational products.

- Prior exposure to tyrosine kinase inhibitor including neratinib, lapatinib, and
afatinib (excluding dacomitinib), or mTOR inhibitor.

Note: There are additional inclusion and exclusion criteria. The study center will
determine if you meet all of the criteria.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response Rate (ORR)

Outcome Description:

ORR is defined as Complete Response (CR) and Partial Response (PR) after receiving at least one prior regimen of chemotherapy

Outcome Time Frame:

minimum 21 days

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2013

Completion Date:

April 2016

Related Keywords:

  • HER2-mutant Non-Small Cell Lung Cancer
  • Lung cancer
  • Puma
  • neratinib
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
University of Colorado Denver, Colorado  80217
Ohio State University Columbus, Ohio  43210
Washington University St. Louis, Missouri  63110
UT Southwestern Dallas, Texas  75390
Dana Farber Boston, Massachusetts  02115-6084
Vanderbilt Nashville, Tennessee  37212
Moffit Tampa, Florida