Exelixis Inc announced top-line results from the final analysis of COMET-2, a randomised, double-blind, controlled trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) who are suffering from moderate to severe pain despite optimised narcotic medication, and whose disease has progressed following treatment with docetaxel as well as abiraterone and/or enzalutamide.

The trial did not meet its primary endpoint of alleviation of bone pain, as determined by comparing the percentage of patients in the two treatment arms who achieved a pain response at Week 6 that was confirmed at Week 12 without increase in narcotic medication. Fifteen per cent of patients in the cabozantinib arm reported a pain response, compared to 17 per cent of patients in the control arm receiving mitoxantrone/ prednisone. The difference in pain response between the arms was not statistically significant. The safety profile of cabozantinib in the trial was consistent with that observed in previous studies in mCRPC.

“Following the COMET-1 top-line results announced in September, we deprioritised the cabozantinib development program in mCRPC; at that time, we also initiated a significant workforce reduction in order to focus our development efforts and financial resources on the pivotal phase 3 studies of cabozantinib in metastatic renal cell carcinoma (RCC) and advanced hepatocellular carcinoma (HCC),” said Michael Morrissey, president and chief executive officer of Exelixis. “With target enrollment in the METEOR study in RCC recently achieved, we anticipate top-line results in the second quarter of 2015. We also look forward to Roche and Genentech’s continued regulatory progress with cobimetinib for metastatic melanoma. The EU review is underway and the US filing is expected before year-end, which could ultimately lead to our opportunity to co-promote cobimetinib in the US if it is approved for this indication.”

Exelixis will submit the results from the COMET programme for potential presentation at a future medical meeting.

COMET-2, the second phase 3 study from the COMET programme, was a randomised, double-blind, controlled trial designed to enroll patients with CRPC that is metastatic to the bone, who were suffering from moderate to severe pain despite optimised narcotic medication, and whose disease had progressed following treatment with docetaxel as well as abiraterone and/or enzalutamide. One hundred and nineteen of the planned 246 patients were randomised 1:1 to receive either cabozantinib or mitoxantrone/prednisone. The primary endpoint was alleviation of bone pain, as determined by comparing the percentage of patients in the two treatment arms who achieve a pain response a greater than or equal to 30 per cent decrease from baseline in the average of daily worst pain intensity according to the BPI collected over seven days at Week 6 that is confirmed at Week 12 without increase in narcotic medication. Secondary endpoints were bone scan response and overall survival, and other endpoints include PFS, safety, and evaluation of bone biomarkers and circulating tumour cells.

Cabozantinib inhibits the activity of tyrosine kinases including MET, VEGFRs and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

COMETRIQ (cabozantinib) is currently approved by the US Food and Drug Administration for the treatment of progressive, metastatic medullary thyroid cancer (MTC).

The European Commission granted COMETRIQ conditional approval for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.