Interim Results of X-396 in ALK positive Non-Small Cell Lung Cancer Appear Promising

Preliminary results from a small phase 1 study of X-396, a novel anaplastic lymphoma kinase (ALK) inhibitor showed that X-396 is well tolerated and has antitumor activity in patients with ALK positive non-small cell lung cancer (NSCLC).

Lung cancer is the leading cause of cancer death in the U.S. and around the world. Up to 7 percent of NSCLC have an abnormal version of the ALK gene that contributes to the growth and development of cancer cells and has recently become the focus for the development of drugs directed at reducing its effect. (2)  Lung cancers with this abnormality typically occur in non-smokers.

X-396 is being developed for the treatment of solid tumors where ALK is deregulated. X-396 has been validated in potency and selectivity assays indicating that it is more selective and up to 10 times more potent than competitive ALK inhibitors. X-396 has been active in animal models of NSCLC and neuroblastoma. Importantly, X-396 has shown activity in ALK mutations that confer resistance to other small molecule ALK inhibitors.

The interim results were recently presented from a dose-escalation phase 1 study evaluating X-396 in patients with advanced solid tumors. The NSCLC patient group was comprised of ALK-positive patients (n=18) who were either Xalkori® (crizotinib)-naïve (n=5) or Xalkori-resistant (n=13). Xalkori is a targeted oral medication that blocks the protein produced by the ALK gene. It works by works by binding with and inhibiting the action of the enzyme that is produced by the mutated gene. Xalkori has become a standard treatment for advanced ALK-positive NSCLC—but most patients will become resistant to it and are left with limited treatment options.

Among 11 ALK positive patients evaluable for response 6 patients had a partial response (55%) and 2 had stable disease (18%). Of the three patients with progressive disease, and acquired resistance to Xalkori anti-cancer activity was also observed

The clinical safety profile for X-396 is thus far favorable and different from other ALK inhibitors. This and other studies are ongoing to better determine what role X-396 will play in the management of NSCLC. X-396 is currently only available through participation in clinical trials.


1.  Horn L, Infante J, Blumenshcein G, et al. A phase I trial of X-396, a novel ALK inhibitor, in patients with advanced solid tumors. J Clin Oncol 32:5s, 2014 (suppl; abstr 8030^)

2.  Shaw AT, Kim DW, Mehra R, et al: Ceritinib in ALK-rearranged non–small-cell lung cancer. New England Journal of Medicine. 2014; 370: 1189-1197.

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