CH5126766 (VS-6766) is a unique inhibitor of the RAS/RAF/MEK/ERK signaling pathway. In contrast to other MEK inhibitors in development, CH5126766 is a dual RAF/MEK inhibitor that blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. In contrast to other MEK inhibitors in development, CH5126766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows CH5126766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.

Clinical Development in Advanced Cancers

Initial signs of activity have been observed in clinical studies as a monotherapy in KRAS mt (mutation) NSCLC, endometrial and ovarian cancers and in BRAF mt ovarian cancer.

Clinical Investigation of CH5126766 Combinations

CH5126766 is currently being evaluated in combination with defactinib for the treatment of several different cancer types with KRAS mutant advanced solid tumors including low grade serious ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) colorectal cancer (CRC) in addition to other tumor types.

Preclinical research by Verastem Oncology scientists and collaborators at world-renowned academic institutions has described the effect of focal adhesion kinase (FAK) inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor.