LY3962673

LY3962673 is a potent, orally bioavailable, and highly selective small molecule inhibitor targeting the GDP-bound form of KRAS G12D. It demonstrates strong selectivity for KRAS G12D over wild-type KRAS and other RAS mutations or amplifications. Preclinical studies have shown robust anti-tumor activity both as a single agent and in combination with other therapies across multiple patient-derived xenograft (PDX) models harboring the KRAS G12D mutation. The drug is currently being evaluated in phase 1 clinical trials (MOONRAY-01) for adults with advanced, unresectable, or metastatic solid tumors that test positive for the KRAS G12D mutation. The primary objectives are to assess safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination regimens. Developed by Loxo Oncology/Eli Lilly, LY3962673 represents a new molecular entity specifically designed to inhibit mutant KRAS G12D—a common oncogenic driver mutation found most frequently in pancreatic (~35%), colorectal (~13%), and non-small cell lung cancers (~4%). There are currently no approved targeted therapies specifically for patients with this mutation. The drug’s development reflects ongoing efforts to address an unmet need in precision oncology.