bbo-11818 + cetuximab

BBO-11818 + cetuximab is an investigational combination therapy for advanced solid tumors with KRAS mutations. BBO-11818 is an orally bioavailable small molecule dual inhibitor targeting the ON (GTP-bound) and OFF (GDP-bound) states of mutant KRAS proteins, notably KRAS G12D, G12V, and G12C, with high specificity and potency. Cetuximab is a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR). The rationale for the combination is that BBO-11818 inhibits multiple mutant KRAS proteins involved in tumor proliferation, while cetuximab blocks EGFR-mediated signaling, potentially enhancing antitumor activity in KRAS-mutant cancers such as non-small cell lung cancer, pancreatic ductal adenocarcinoma, and metastatic colorectal cancer. The combination is under investigation in phase 1 trials for safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with unresectable or metastatic KRAS-mutant solid tumors, especially in dose expansion cohorts.