Case History

Xalkori™ (crizotinib, PF-02341066), a receptor tyrosine kinase (RTK) inhibitor targeting mesenchymal epithelial transition (MET)/anaplastic lymphoma kinase (ALK), was invented using structure-based drug design and medicinal chemistry lead optimization. The U.S. Food and Drug Administration granted fast-track approval of crizotinib on August 26, 2011 based on the marked efficacy of crizotinib in patients with ALK-positive advanced non-small cell lung cancer (NSCLC) and good safety profile in Phases I and II trials. Promising antitumor activity has been observed with crizotinib in patients with abnormal ALK genes of anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, and neuroblastoma; with abnormal ROS1 gene in NSCLC; and with MET gene amplified NSCLC. The broad antitumor activities of crizotinib based on molecular targets across many cancers indicate the importance of understanding tumor biology to identify the oncogenic driver targets for the stratification of the right patient population.