Pfizer’s supplemental new drug application for Xalkori (crizotinib) has been approved by the U.S. FDA for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC). The drug is also indicated for patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

The ROS1 gene codes for a receptor tyrosine kinase (RTK) of the insulin receptor family. ROS1 rearrangements, or fusions, where the ROS1 gene attaches to another gene changing its normal function and activating pathways related to cell proliferation and growth, have been shown to be a potential “driver” mutation in NSCLC subtype, which comprises 85 to 90 percent of all lung cancers. According to My Cancer Genome, about 2 percent of NSCLC tumors harbor ROS1 fusions.

Xalkori, which has been used to treat more than 8,000 patients to date, is a kinase inhibitor indicated in the U.S. for the treatment of patients with NSCLC whose tumors are ALK-positive as detected by an FDA-approved test, and for the treatment of patients with metastatic NSCLC whose tumors are ROS1-positive. It has become the first ALK inhibitor approved in the U.S.

The recent approval is based on results from a multicenter, single-arm, Phase 1 study (Study 1001), where 50 patients with ROS1-positive metastatic NSCLC were treated with 250 mg of Xalkori orally twice daily. Primary outcomes included objective response rate and duration of response. The results showed that Xalkori displayed anti-tumor activity in patients with ROS1-positive metastatic NSCLC, with an objective response rate of 66 percent and a median duration of response of 18.3 months. Researchers observed one complete response and 32 partial responses.

Researchers believe the drug’s approval is an important step forward in biomarker-driven cancer care, allowing the definition of a distinct subset of patients for whom Xalkori is effective. A diagnostic test is under development for the identification of patients with ROS1-positive metastatic NSCLC. Moreover, the European Medicines Agency (EMA) is reviewing an application to extend the marketing authorization of Xalkori to include the treatment of adult patients with ROS1-positive advanced NSCLC.

“Today’s approval of Xalkori for ROS1-positive metastatic NSCLC represents an important milestone for patients who previously had limited treatment options,” Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology, said in a press release. “As the only FDA-approved biomarker-driven therapy that includes two distinct molecular targets in metastatic NSCLC, ROS1 and ALK, Xalkori exemplifies our commitment to precision drug development and to identifying the right treatment for the right patient.”