Today (October 24), the China State Drug Administration Drug Evaluation Center (CDE) official website latest public announcement, Class 1 new drug GFH925 (IBI351) tablets to be included in the priority review, for the indication: treatment of at least one systemic treatment of KRAS G12C mutant advanced non-small cell lung cancer (NSCLC). GFH925 is a KRAS G12C inhibitor, according to public information. The product's indication for treating patients with advanced NSCLC and colorectal cancer with KRAS G12C mutant phenotype who have received at least one systemic therapy has previously been included in the Breakthrough Therapy assortment by the CDE.
GFH925 is a highly potent oral novel molecular entity compound that effectively inhibits protein-mediated GTP/GDP exchange by covalently and irreversibly modifying cysteine residues of the KRAS G12C protein mutant, thereby downregulating the level of KRAS protein activation; preclinical cysteine-selective testing has also demonstrated the highly selective inhibitory efficacy of GFH925 at this mutation site. In addition, the inhibition of KRAS protein by GFH925 can inhibit the downstream signaling pathway, effectively inducing apoptosis and cell cycle blockade of tumor cells to achieve anti-tumor effects.
In September 2021, Cinda Biotech and Jinfang Pharmaceutical announced an exclusive worldwide license agreement, under which Cinda Biotech will be the exclusive partner to obtain the development and commercialization rights of GFH925 in China (including Mainland China, Hong Kong, Macau and Taiwan), with an option for global development and commercialization rights. Jinfang Pharmaceutical is responsible for the supply of the drug production in the clinical research stage and the commercialization stage of the drug. According to public information, the amount involved in this licensing cooperation is more than 300 million US dollars.
According to the CDE announcement, GFH925 tablets are proposed to be included in the priority review for the indication of advanced NSCLC with KRAS G12C mutation.Lung cancer is the most common type of cancer, of which NSCLC accounts for about 80% to 85% of lung cancer cases. Most NSCLC patients carry different genetic mutations, and KRAS G12C mutation is one of the common mutations (about 13%). NSCLC patients with this mutation are usually resistant to other targeted drugs and often have a poor prognosis, therefore, these patients are in urgent need of targeted therapies.
Previously, Cinda Biotech has presented updated results from a Phase 1a study of GFH925 monotherapy in patients with advanced solid tumors in an oral presentation at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting. As of July 29, 2022, the study enrolled 67 subjects with advanced malignancies who had previously failed or were intolerant to standard therapy, including 61 with non-small cell lung cancer. Nearly 50% of the subjects had received 2 or more lines of prior therapy, and 37.7% of the lung cancer patients had brain metastases at baseline.
The study results showed that in the 55 non-small cell lung cancer efficacy assessable population, the objective remission rate (ORR) was 50.9% and the disease control rate (DCR) was 92.7%; the vast majority of patients in remission were still on ongoing treatment; the low-dose group showed sustained tumor remission right away, and the longest duration of treatment had been up to 8.9 months (450mg once-a-day dosage group) and was still on ongoing treatment; Median duration of remission and median progression-free survival were not reached.The 600 mg twice-a-day dose group (phase 2 recommended dose) presented superior efficacy, with an objective remission rate (ORR) and disease control rate (DCR) of 61.9% (13/21) and 100%, respectively, in 21 evaluable subjects.
In terms of safety, as of the date of data analysis, the overall tolerability was good, with no dose-limiting toxicity (DLT) events observed in the dose groups, and MTDs were not reached. A total of 92.5% (62/67) of subjects experienced drug-related adverse events (TRAEs), the majority of which were grade 1-2, with the most common TRAEs being anemia, elevated aminotransferases, and elevated bilirubin, pruritus, and malaise.Grade ≥3 TRAEs were observed in 19.4% of subjects, and there were no TRAEs that resulted in death, as well as TRAEs leading to treatment discontinuation.