AMG 410 + pembrolizumab

AMG 410 + pembrolizumab is an investigational combination therapy being studied for the treatment of advanced or metastatic solid tumors with KRAS alterations. AMG 410 is a small-molecule, oral, reversible, non-covalent pan-KRAS inhibitor developed by Amgen, showing biochemical potency across numerous KRAS missense mutations and designed to inhibit both GDP- and GTP-bound forms of KRAS while sparing HRAS/NRAS. It inhibits the ERK signaling pathway in preclinical cancer models. Pembrolizumab is an approved humanized monoclonal antibody against PD-1, functioning as a checkpoint inhibitor to restore antitumor immunity. The combination aims to leverage targeted KRAS inhibition alongside immune checkpoint blockade to improve efficacy in KRAS-mutant cancers. The ongoing Phase 1/1b trial assesses safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity for this combination in a dose-escalation and expansion format, with recruitment across multiple solid tumor types (including NSCLC, colorectal cancer, and pancreatic ductal adenocarcinoma)[1][2][3].