PF-07284892 + binimetinib

PF-07284892 + binimetinib is a **combination therapy** composed of the investigational allosteric SHP2 inhibitor PF-07284892 and binimetinib, a clinically approved MEK inhibitor. PF-07284892 selectively and potently inhibits the **SHP2 phosphatase** to block signaling downstream of various oncogenic drivers (e.g., BRAF, KRAS, ALK, ROS1), overcoming both primary and secondary resistance to targeted therapies by suppressing reactivation of the MAPK pathway. Binimetinib inhibits **MEK1/2 kinases** to further block MAPK/ERK pathway activity. This combination is used in patients with advanced solid tumors harboring resistance mutations (such as BRAF^V600E^ or KRAS^G12D^) to targeted therapies, where monotherapy with either agent is insufficient. In Phase I studies, the combination has shown **partial responses and tumor regression** in some cases where patients previously failed similar targeted agents, supporting synergistic suppression of oncogenic signaling[1][2][3].