Exelixis commences cabozantinib phase 3 pivotal trial in mCRPC

Exelixis, Inc. (NASDAQ:EXEL) today announced the initiation of COMET-1, a phase 3 pivotal trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint for COMET-1 is overall survival (OS) in mCRPC patients who have had disease progression after treatment with docetaxel and abiraterone acetate and/or MDV3100. Exelixis expects data from COMET-1 to be available in the first half of 2014.

"COMET-1 is a well-designed global study of a compound with the potential to address many of the unmet medical needs for men with mCRPC," said Matthew R. Smith, M.D., Ph.D., director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center and lead investigator for COMET-1. "The phase 2 studies of cabozantinib provide early evidence of impressive effects on measurable tumor, progression-free survival, bone scan response, pain alleviation, and circulating tumor cell (CTC) counts. Several of these measures, including reduction in pain and CTC counts, are associated with improved overall survival in mCRPC. If COMET-1 confirms these early findings and demonstrates a survival benefit, I believe cabozantinib could become an important new treatment option for men with mCRPC."

COMET-1 is a double-blind, placebo-controlled phase 3 study that will include up to 240 international sites. The trial is designed to enroll 960 patients with mCRPC who have previously been treated with docetaxel, and abiraterone acetate and/or MDV3100. All patients will have bone metastases and there is no limit to the number or type of prior treatments. Patients will be randomized 2:1 to receive cabozantinib (60 mg daily, N=640) or prednisone (5 mg twice daily, N=320). Each arm will also receive placebo in order to account for the once-daily versus twice-daily dosing regimens of cabozantinib and prednisone. The trial has 90% power to detect a 25% reduction in the risk of death (HR = 0.75). The final analysis will be event driven, with 578 events required. A single interim analysis is planned after 387 events. The secondary endpoint is bone scan response as assessed by an independent radiology facility (IRF).

"The initiation of the COMET-1 trial, which is focused on demonstrating the potential for cabozantinib to improve overall survival in mCRPC patients, is an important milestone in the cabozantinib development program in prostate cancer," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "A successful outcome for COMET-1 and for the ongoing COMET-2 pivotal trial would document the ability of cabozantinib to extend survival and to provide significant pain palliation in mCRPC, a distinct and differentiated profile that we believe provides the best opportunity to maximize cabozantinib's clinical and commercial potential."