The MEK inhibitor Mekinist (trametinib) is to be tested in combination with Opdivo (nivolumab) — or Opdivo plus Yervoy (ipilimumab) — in colorectal cancer patients with microsatellite stable tumors under a clinical collaboration between Novartis and Bristol-Myers Squibb. The Phase 1/2 trial will aim to establish the recommended dose regimens and an early assessment of the effectiveness of the two combinations. The study will test the therapies in patients with metastatic and microsatellite stable colorectal cancer, whose tumors have a fully functional DNA repair mechanism. Results will help determine the best approaches for further studies into these combination treatments. Under the terms of the agreement, Bristol Myers-Squibb will be responsible for conducting the study. "Novartis has a longstanding heritage in exploring the combination of medicines to broaden our knowledge of mutational driven cancers and develop innovative treatments," Vas Narasimhan, MD, head, global drug development and chief medical officer, Novartis, said in a press release. "Along with our ongoing internal immuno-oncology efforts, the expansion of our collaboration with Bristol-Myers Squibb further advances our collective goals to advance the science and to support patients in need." Mekinist targets the MEK1/2 proteins, key molecules in the MAPK signaling pathway that is critical for the proliferation, differentiation, and formation of new blood vessels. These proteins have been implicated in colorectal and other cancer types. Opdivo is an inhibitor of the programmed cell death (PD)-1 protein, a molecule that plays an important role in preventing the immune system from targeting and destroying cells. By blocking PD-1, Opdivo unleashes certain immune cells, allowing them to effectively attack tumor cells. Opdivo is a treatment option across multiple cancers, including metastatic colorectal cancer. Yervoy is a checkpoint inhibitor that, similar to Opdivo, blocks molecules known as immune checkpoints. Cancers often use the checkpoints to evade attack by the immune system. 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 a cell's ability to repair its DNA during cell division.