NCCN Request for Proposals (RFP): Phase I/II Clinical and/or Correlative Studies of the panHER Inhibitor Neratinib in the Treatment of Breast, Gastrointestinal, Lung, and Neurological Cancers

Funding Agency:
National Comprehensive Cancer Network

The National Comprehensive Cancer Network (NCCN) has received a $2 Million Dollar research grant from Puma Biotechnology (hereafter, “Grantor”) to support NCCN Member Institution faculty for the performance of clinical and correlative studies to further evaluate the effectiveness of neratinib in the treatment of breast, gastrointestinal (GI), lung and neurological cancers. NCCN will serve as the funding organization. Grants are available only to investigators from NCCN Member Institutions.

Neratinib is an anilinoquinoline derivative intracellular oral kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4. In vitro, neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7, and M11 inhibited the activity of EGFR, HER2, and HER4 in vitro. In vivo, oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR. A comprehensive review article has been published that investigators can review for additional preclinical information on neratinib.

The overall aim is to develop innovative studies to help determine the role of neratinib for breast, GI, lung and certain neurological cancers. It is hoped proposals submitted in response to this RFP should be useful in guiding further clinical development of neratinib. Clinical studies with correlative endpoints are encouraged.

Deadline: April 19, 2021




Medical - Clinical Science

External Deadline

April 19, 2021