Study of the mass balance, biotransformation, and safety of ¹⁴CIBI351 in healthy Chinese subjects

IBI351, a synthetic compound, exerts its anti-tumor effects by specifically, covalently, and irreversibly modifying the 12th cysteine residue of KRAS G12C. However, the pharmacokinetic profile of IBI351 in humans has not yet been reported. The current study aimed to investigate the pharmacokinetics and safety of IBI351 in healthy Chinese male subjects. A single oral dose of 600 mg combined with 150 μCi ¹⁴CIBI351 was administered to six healthy male volunteers. Blood, urine, and fecal samples were collected at multiple time points to quantify the parent drug and its metabolites. IBI351 showed favorable pharmacokinetic characteristics and was well tolerated by all participants. Seventeen major metabolites were identified in plasma, urine, and feces. The main metabolic pathways included oxidation, hydrogenation, sulfonate conjugation, glucuronide conjugation, and cysteine conjugation. Excretion of IBI351 and its metabolites occurred mainly through feces. Collectively, this first-in-human study provides essential data on the metabolism and safety of IBI351 in Chinese subjects and lays the foundation for its further clinical development as a novel anti-tumor drug.