Pfizer to commence Phase 3 trial of oral c-Met and ALK inhibitor

Pfizer Oncology announced today that it will initiate a global, Phase 3 clinical trial of its investigational oral c-Met and ALK inhibitor, PF-02341066, versus standard of care chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) carrying the ALK (anaplastic lymphoma kinases) fusion gene, who have progressed on one prior treatment with a platinum-based chemotherapy. Updated data from an expansion cohort of a Phase 1 study with PF-02341066 in NSCLC patients with tumors carrying this fusion gene were featured today at the ECCO15/ESMO34 meeting in Berlin, Germany (Abstract #6G).

PF-02341066 is an investigational, selective, ATP-competitive small molecule dual inhibitor of mesenchymal epithelial transition growth factor (c-Met or hepatocyte growth factor) and ALK tyrosine kinases, which are implicated in the progression of several cancers, including NSCLC. A subset of NSCLC patients have been identified whose tumors carry a unique mutation in which the echinoderm microtubule-associated protein-like 4 (EML4) gene is fused to ALK, also known as an EML4-ALK translocation. This fusion/translocation has been reported in 3–7 percent of all NSCLC patients, with the incidence increasing to 10-20 percent among NSCLC patients with adenocarcinoma histology and those who have a never-to-light smoking history, and represents one of the newest molecular targets in NSCLC.

“We see this as an extraordinary opportunity for rational drug development. This represents a shift from large trials designed to detect a small benefit in a large group of patients towards looking for a bigger effect in a smaller, better characterized group of patients. By focusing on the subset of patients whose lung cancers carry the EML4-ALK translocation, we will be in the best position to determine the clinical effects of PF-02341066, both good and bad, in comparison to standard chemotherapy,” said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer’s Oncology Business Unit.