cobimetinib + GDC-0994

The combination of **cobimetinib** (a selective MEK1/2 inhibitor) and **GDC-0994** (a selective ERK1/2 inhibitor) targets two key nodes of the mitogen-activated protein kinase (MAPK) pathway, which is frequently dysregulated in various solid tumors, particularly those with RAS or RAF mutations. Simultaneous inhibition of MEK and ERK has demonstrated enhanced suppression of MAPK pathway output, more potent anti-tumor activity, and increased cell death in preclinical models of KRAS- or BRAF-mutant cancers compared to inhibition of either node alone. In clinical phase Ib trials in patients with advanced or metastatic solid tumors, this oral combination showed classical MAPK-inhibitor adverse events, but overlapping and cumulative on-target toxicity limited tolerability and further clinical development[1][2][3][4][5]. Cobimetinib was developed by Genentech/Roche, and GDC-0994 was developed by Genentech.

Other names

cobimetinib + GDC-0994