KRAS mutation is one of the most common driver gene mutations in non-small cell lung cancer (NSCLC). KRAS was once considered a "difficult to drug" target, but with the successive approval of KRAS inhibitors such as sotorasib and adagrasib for the treatment of NSCLC patients carrying KRAS mutations, anti-cancer therapies targeting specific KRAS gene mutations have become one of the highly anticipated clinical research directions.
Glecirasib is a KRASG12C allosteric inhibitor. Previous Phase 1 studies have found that Glecirasib has good anti-tumor activity and tolerability against solid tumors (mainly NSCLC) carrying KRASG12C mutations.
Recently, a study published in Nature Medicine showed that for NSCLC patients with locally advanced or metastatic KRASG12C mutations, the objective response rate (ORR) and disease control rate (DCR) after treatment with Gleanercept were 47.9% and 86.3%, respectively. The corresponding author of this study is Professor Shi Yuankai from the China National Cancer Center/China National Cancer Clinical Research Center/Cancer Hospital of the Chinese Academy of Medical Sciences.
This is an open label, monotherapy, phase 1/2 study conducted in 41 medical centers in China, which included 119 NSCLC patients with locally advanced or metastatic KRASG12C mutations. The median age of the patients was 62 years old, with 16.8% of patients having brain metastases at baseline and 48.7% of patients having received second-line or higher anti-cancer treatment. All patients received at least a single dose of oral administration of 800 mg of goserese.
As of March 28, 2024, there are still 41 patients receiving study treatment, with a median follow-up time of 10.4 months.
The research results showed that the ORR evaluated by the independent review committee was 47.9% (95% CI: 38.5%~57.3%), reaching the primary endpoint of the study.
In terms of secondary endpoints, the relevant indicators are as follows:
DCR：86.3%(95%CI：78.7%~92.0%);
Median time from treatment to onset of remission (TTR): 1.4 months (95% CI: 1.2-9.8);
Median duration of response (DoR): Immature (95% CI: 7.2 months to non evaluable);
Median progression free survival (PFS): 8.2 months (95% CI: 5.5~13.1);
Median OS: As of the deadline, a total of 33.6% of enrolled patients died, with a median OS of 13.6 months (95% CI: 10.9~not evaluable).
In terms of safety, the incidence of treatment-related adverse events at any level is 97.5%, with the main adverse events being anemia and elevated blood bilirubin. The overall security is controllable.
In summary, the results of this study indicate that the use of goserecept in NSCLC patients with locally advanced or metastatic KRASG12C mutations has shown promising efficacy and manageable safety features.
<Reprinted from WuXi AppTec>
