Jingfang Pharma Launches IPO: Developer of China's First KRAS G12C Inhibitor Fuzeleresib (IBI351)

On November 24, the CDE website showed that the marketing application for IBI351 (Fulzerasib tablets), a KRAS G12C inhibitor co-developed by Innovent Bio and Genfleet Therapeutics, has been accepted. The indicated indication is for the treatment of advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation in patients who have received at least one prior systemic therapy. The application had previously been granted priority review.

The acceptance of this New Drug Application (NDA) and its inclusion in the priority review program are based on the results of a Phase II single-arm registration-enabling clinical study conducted in China (NCT05005234). The study aimed to evaluate the safety, tolerability, and efficacy of IBI351 monotherapy in subjects with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations who had failed or were intolerant to standard therapy. The results of the registration-enabling study were scheduled to be presented at the European Society for Medical Oncology Asia Congress 2023 (ESMO ASIA 2023).

IBI351 is a specific covalent irreversible KRAS G12C inhibitor that effectively inhibits the protein-mediated GTP/GDP exchange, thereby downregulating the activation level of the KRAS protein. Preclinical cysteine selectivity assays also demonstrated that foruzesertib exhibits highly selective inhibitory potency against this mutation site.

In September 2021, GenFleet Therapeutics and Innovent Bio entered into a strategic collaboration, whereby Innovent Bio, as the exclusive partner, obtained the rights to develop and commercialize GFH925 in China, along with an option for global development and commercialization rights.

Previously, the results of the Phase I clinical study of IBI351 monotherapy in patients with advanced solid tumors were presented as an oral report at the 2023 American Association for Cancer Research Annual Meeting (AACR 2023). The data showed that, as of February 10, 2023, among 67 efficacy-evaluable patients with non-small cell lung cancer, the objective response rate (ORR) was 61.2%, and the disease control rate (DCR) was 92.5%.

Among them, the 600 mg BID dose group (recommended phase 2 dose, RP2D) demonstrated superior efficacy. Among 30 evaluable subjects, the objective response rate (ORR) was 66.7% (20/30), with a confirmed objective response rate (cORR) of 53.3% (16/30). The disease control rate (DCR) was 96.7%. The median duration of response (mDOR) was not reached, and the 6-month DOR rate was 75.4% (95% CI, 39.8–91.7). The median progression-free survival (mPFS) was 8.2 months, with a PFS event rate of 46.7% (14/30). The 6- and 9-month progression-free survival rates were 58.9% (95% CI, 39.0–74.3) and 47.3% (95% CI, 26.1–65.8), respectively. The median follow-up time was 8.1 months, and the data are not yet mature.

In terms of safety, as of November 30, 2022, the overall tolerability was favorable. No dose-limiting toxicity (DLT) events were observed across all dose groups, and the maximum tolerated dose (MTD) was not reached. Treatment-related adverse events (TRAEs) occurred in 94.0% (63/67) of subjects, most of which were Grade 1–2. The most common TRAEs included anemia, pruritus, elevated transaminases, fatigue, proteinuria, and hyperbilirubinemia. Grade ≥3 TRAEs occurred in 31.3% of subjects, with no TRAEs leading to treatment discontinuation or death.