J Biomed Res
Phase I Clinical Trial Unit, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Published: September 2024
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 characteristics of IBI351 in the human body have not 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/150 μCi [ C]IBI351 was administered to six healthy male subjects. Blood, urine, and fecal samples were collected at continuous time points to analyze the levels of IBI351 parent drug and its metabolites. We found that IBI351 showed favorable pharmacokinetic characteristics, and was well tolerated in all the six participants. In addition, 17 major metabolites of IBI351 were analyzed and identified in the blood, urine, and feces. The main metabolic pathways included oxidation, hydrogenation, sulfonate conjugation, glucuronide conjugation, and cysteine conjugation. IBI351 and its metabolites were primarily excreted through feces. Taken together, this is the first study on the metabolism and safety of IBI351 in Chinese subjects, and these findings may guide future clinical development of IBI351 as a novel anti-tumor drug.
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http://dx.doi.org/10.7555/JBR.38.20240254 | DOI Listing |
J Thorac Oncol
January 2025
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, People's Republic of China. Electronic address:
J Thorac Oncol
January 2025
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, People's Republic of China. Electronic address:
J Biomed Res
September 2024
Phase I Clinical Trial Unit, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Eur J Cancer
November 2024
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. Electronic address:
J Thorac Oncol
December 2024
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China. Electronic address:
Introduction: KRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study.
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