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12:00 AM
 | 
Apr 25, 2011
 |  BioCentury  |  Product Development

In with the ALK Crowd

Pfizer's crizotinib for NSCLC spurs Tesaro's ALK inhibitor deal with Amgen

Pfizer Inc.'s crizotinib has provided POC that targeting ALK can significantly improve response in a small subset of non-small cell lung cancer patients compared to current treatments. While the pharma completes it NDA submission, other companies are lining up behind it with second-generation programs that they believe will be more selective and more potent.

One of them is a newco, Tesaro Inc., which in-licensed Amgen Inc.'s ALK program last month.

In January, Pfizer began submission of a rolling NDA to FDA for crizotinib (PF-02341066). It is an oral small molecule dual inhibitor of c-Met receptor tyrosine kinase and anaplastic lymphoma kinase (ALK) and their oncogenic variants.

According to Darrel Cohen, senior director of oncology clinical development, the pharma originally planned to develop the small molecule based on its c-Met inhibitory properties because "we felt that was an important oncogenic driver in a number of solid tumor types."

In 2007, however, researchers at Jichi Medical University published in Nature that constitutive expression of a fusion gene containing portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK may be an alternate oncogenic driver of NSCLC. The researchers found the ELM4-ALK mutation in 6.7% of patient tumor samples analyzed.

At around the same time, Cohen said Pfizer saw objective responses in two "heavily pretreated" NSCLC patients in a Phase I trial of crizotinib. The ORR results, coupled with the information published in Natureand the absence of c-Met amplification, suggested the EML4-ALK fusion protein and not c-Met might be a more important target in a subset of patients with that...

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