July 29, 2021 -- GenFleet Therapeutics, a clinical-stage biotechnology company developing cutting-edge therapies in oncology and immunology worldwide, today announced that the National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for GFH925 in a multi-center phase I / II clinical trial treating advanced solid tumors among patients with KRAS G12C gene mutation.
Designed to treat advanced non-small cell lung cancer and gastrointestinal cancer, the clinical trial sets its primary objective to evaluate the safety/tolerability and efficacy, and to characterize the pharmacokinetics of GFH925 in patients with KRAS G12C gene mutation. By profiling the gene mutations in tissue & blood samples, the study will include information both in baseline assessment and after disease progression. Moreover, the trial will explore the potential mechanisms of primary and acquired resistance to KRAS inhibitors.
“As a frequently altered proto-oncogene, RAS mutation is widespread among patients of non-small cell lung cancer, pancreatic cancer, colorectal cancer, etc. Around 80% of KRAS mutation subtypes occur in codon 12; in addition, G12C mutations amount to 1/3 of all KRAS G12C mutations with poor prognosis. Our development scheme will be built upon the trial data and the resistance mechanism research of other KRAS inhibitors, while referring to the epidemiological data in China. Based on biomarkers obtained in the trial, we will also optimize our precision treatment plans and pave the way for the potential of combination therapies.” said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet Therapeutics.
“RAS used to be an undruggable target and the basic research of RAS protein has spanned decades. There was no KRAS G12C inhibitor moving into clinical trials when we started our program, which is consistent with GenFleet’s mission of developing cutting-edge products with novel mechanisms. Preclinical data sufficiently differentiated GFH925 from other KRAS G12C inhibiting products, and our strategy highly conforms to the latest industrial initiative of providing better options for patients as the ultimate goal of drug discovery and development. We look forward to continuous progress of our pipeline and better healthcare solution for patients worldwide.” said Jiong Lan, Ph.D., Co-founder and Chief Executive Officer of GenFleet Therapeutics.
About KRAS & GFH925
RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and TRK 1/2/3 mutations combined.
By covalently and irreversibly modifying the cysteine residue of KRAS G12C protein, GFH925 inhibits the GTP/GDP exchange, an essential step in pathway activation. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.