Exelixis’ Phase III prostate cancer trial of cabozantinib fails to meet primary endpoint

1st September 2014 (Last Updated September 1st, 2014 18:30)

US-based biopharmaceutical firm Exelixis has reported disappointing top-line results from the final analysis of COMET-1, the Phase III trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC).

Prostate cancer with Gleason pattern 4 low mag

US-based biopharmaceutical firm Exelixis has reported disappointing top-line results from the final analysis of COMET-1, the Phase III trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC).

The trial evaluated cabozantinib in mCRPC patients whose disease progressed after treatment with docetaxel as well as abiraterone and/or enzalutamide.

The company said that the trial failed to meet its primary endpoint of showing a statistically significant increase in overall survival (OS) for patients treated with cabozantinib as compared to prednisone.

The median OS for the cabozantinib arm of the Phase III trial was 11 months versus 9.8 months for the prednisone arm.

Exelixis president and chief executive officer Michael Morrissey said: "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 programme 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."

Results from the COMET-1 are the subject of ongoing analyses and the company intends to submit additional data, including secondary and exploratory endpoints, for presentation at a future medical meeting.

"We are very disappointed that COMET-1 did not meet its primary endpoint of extending overall survival in men with mCRPC."

In addition to OS, the exploratory endpoint of progression-free survival (PFS) as evaluated by the investigators is the only time-to-event-based endpoint for which data are available.

Based on the outcome of the COMET-1 trial, the company now intends to start a significant workforce reduction that will help in focusing on its financial resources on the late-stage clinical trials of cabozantinib in metastatic renal cell carcinoma (the METEOR trial) and advanced hepatocellular carcinoma (the CELESTIAL trial).

As a result of the outcome of trial, the company has deprioritised the clinical development of cabozantinib in mCRPC.

Patient enrolment has been stopped in COMET-2, a second major trial in mCRPC and evaluates pain palliation.

The company said that based on the outcome of COMET-2 trial, it will carry out discussions with regulatory authorities about the potential regulatory path, if any, of cabozantinib in mCRPC.

Other company-sponsored mCRPC trials, including a randomised Phase II trial of cabozantinib in combination with abiraterone, will also be stopped.


Image: Micrograph of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Photo: courtesy of Nephron.