Exelixis, Inc. has announced the results from its COMET-1 phase 3 trial on cabozantinib for the treatment of metastatic castration-resistant prostate cancer (mCRPC) did not meet the primary endpoint of overall survival (OS) when compared with prednisone treatment.
Cabozantinib (COMETRIQ) is a U.S. Food and Drug Administration approved drug for the treatment of progressive, metastatic medullary thyroid cancer, which inhibits the activity of tyrosine kinases involved in both normal cellular functions and pathologic oncogenic processes such as metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.
COMET-1 was a randomized, double-blind, controlled trial that enrolled 960 patients with mCRPC suffering from bone metastases, who had previously been treated with docetaxel, abiraterone or enzalutamide, and whose cancer progressed after treatment. Patients were randomized to receive either cabozantinib or prednisone, an immunosuppressant corticosteroid.
The primary endpoint of the trial was set to OS, and the secondary endpoint was bone scan response as assessed by an independent radiology committee.
The COMET-1 results are still under analysis since in addition to OS, progression-free survival (PFS) is the only time-to-event-based endpoint for which data are available, with a median PFS of 5.5 months for the cabozantinib arm versus 2.8 months for the prednisone arm.
“We are very disappointed that COMET-1 did not meet its primary endpoint of extending overall survival in men with mCRPC. We are grateful to the patients, physicians, nurses, caregivers, and other study team members who participated in the trial. We remain focused on the development program for cabozantinib beyond mCRPC, including the ongoing METEOR and CELESTIAL phase 3 pivotal trials, from which we expect top-line data in 2015 and 2017, respectively,” Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis stated in a company’s press release.
Based on these results, Exelixis has deprioritized the clinical development of cabozantinib in mCRPC . However, by the end of 2014, the company will evaluate the data from COMET-2, the second pivotal trial in mCRPC evaluating pain palliation, and decide the potential regulatory path of cabozantinib in mCRPC.