alectinib + cobimetinib

Alectinib + cobimetinib is a combination therapy being investigated for the treatment of ALK-positive non-small cell lung cancer (NSCLC). This combination targets two different pathways: alectinib inhibits the anaplastic lymphoma kinase (ALK) protein, while cobimetinib inhibits the MEK protein in the mitogen-activated protein kinase (MAPK) pathway. The rationale for this combination is to address ALK-independent resistance mechanisms that often develop in ALK+ lung cancers through reactivation of the MAPK signaling pathway. In clinical trials, the combination has shown limited activity in alectinib-resistant tumors but demonstrated durable responses in alectinib-naïve patients, despite some dose-limiting toxicities including dermatologic issues and muscle enzyme elevations.