The MEK inhibitor binimetinib will soon be tested in combination with Opdivo (nivolumab) plus Yervoy (ipilimumab) in colorectal cancer patients with microsatellite stable tumors, under a clinical collaboration between Array BioPharma and Bristol-Myers Squibb.
“Array is pleased to announce this new collaboration with Bristol-Myers Squibb,” Array CEO Ron Squarer said in a news release. “Based on emerging data, we believe that studying combinations of targeted therapies such as binimetinib with immuno-oncology agents, such as Opdivo and Yervoy, could provide important scientific advances for patients fighting cancer.”
MEK is a key protein in the MAPK signaling pathway, which is crucial to the proliferation, differentiation, survival and generation of new blood vessels. This protein often overreacts in melanomas as well as colorectal and thyroid cancers, among others, leading to uncrontrolled cell growth.
The BEACON CRC Phase 3 trial (NCT02928224) is currently evaluating binimetinib in combination with Array’s BRAF inhibitor encorafenib and Erbitux (cetuximab) in BRAF V600E-mutant colorectal cancers. The two companies are now analyzing the potential of combining binimetinib with immunotherapies, which have shown only limited benefit in colorectal cancers.
The Phase 1/2 trial, expected to begin in the second half of 2017, aims to establish the recommended Phase 2 dose regimens and assess preliminary efficacy of the binimetinib-Opdivo-Yervoy triple combo. The study will enroll colorectal cancer patients with microsatellite stability, with results to determine optimal approaches in further studies assessing this combination regimen.
“Colorectal cancer remains a challenging tumor where immunotherapy benefits have been limited to a subset of patients,” said Dr. Fouad Namouni, head of oncology development at Bristol-Myers Squibb. “We are committed to investigating a wide range of oncology therapies, and look forward to studying the combination of Array’s MEK inhibitor and our immunotherapies with the goal of developing more treatment options for patients.”
Colorectal cancer is the third most common type of cancer in men, and the second most common in women. In 2017 alone, more than 135,000 Americans will be newly diagnosed with either colon or rectal cancer. Microsatellite stability is defined as the absence of changes in the number of short, repeated sequences of DNA, know as microsatellites. Usually, microsatellite instability is linked to defects in the cells’ ability to repair their DNA during cell division.