China’s Center for Drug Evaluation of the National Medical Products Administration has granted a breakthrough therapy designation to glecirasib for the treatment of patients with pancreatic cancer harboring a KRAS G12C mutation and who have progressed after frontline standard-of-care treatment.
China’s Center for Drug Evaluation (CDE) of the National Medical Products Administration has granted a breakthrough therapy designation (BTD) to glecirasib (JAB-21822) for the treatment of patients with pancreatic cancer harboring a KRAS G12C mutation and who have progressed after frontline standard-of-care (SOC) treatment.1
The BTD was based on the clinical efficacy and safety data from ongoing clinical trials evaluating the agent. In July 2023, the CDE approved a pivotal trial of glecirasib, making it the first global KRAS G12C–mutated pancreatic cancer registrational clinical study, according to Jacobio Pharma. The multicenter, single-arm, open-label study will evaluate the agent in patients with KRAS G12C–mutated, locally advanced or metastatic pancreatic cancer that has progressed on frontline standard-of-care treatment.
In December 2022, glecirasib received a BTD in China as a potential option in the second-line setting and beyond for patients with advanced or metastatic non–small cell lung cancer (NSCLC) harboring a KRAS G12C mutation.
Additionally, data from a prior first-in-human phase 1/2 trial (NCT05009329) showed that glecirasib was well tolerated with no dose-limiting toxicities in patients with KRAS G12C–mutated advanced solid tumors, including NSCLC and pancreatic cancer.2 The agent also demonstrated preliminary efficacy in this population.
Among all evaluable patients (n = 49), the overall response rate was 40.8%, and the disease control rate (DCR) was 91.8%. Among patients with NSCLC (n = 32), the ORR and DCR were 56.3% and 90.6%, respectively. In those with NSCLC who were treated with 400 mg or 800 mg of glecirasib per day (n = 12), the ORR and DCR were 66.7% and 100%, respectively.
Regarding safety across all cohorts (n = 72), the most common adverse effects (AEs) reported in at least 10% of patients included increased blood bilirubin, anemia, increased alanine transaminase, increased aspartate transaminase, and proteinuria. The majority of treatment-related AEs (TRAEs) were grade 1 or 2, and fewer grade 3/4 TRAEs were reported with once-daily dosing compared with 2 or 3 doses per day. No grade 5 TRAEs occurred, and no patients discontinued treatment due to TRAEs. Three patients (4.2%) experienced serious AEs.
The study enrolled patients with advanced or metastatic solid tumors harboring a KRAS G12C mutation who were refractory or intolerant to SOC treatment or were not willing to undergo standard treatment. Patients also needed to have measurable disease per RECIST v1.1 criteria, no active brain or spinal metastases, an ECOG performance status of 0 or 1, and adequate organ function. In the NSCLC expansion cohort, no more than 3 prior lines of therapy were allowed.
During dose escalation, patients received glecirasib at 200 mg per day (n = 5), 400 mg per day (n = 18), 800 mg per day (n = 22), 400 mg twice per day (n = 12), and 400 mg thrice per day (n = 15).
The objectives of the study were to evaluate the safety and tolerability of glecirasib, determine the maximum tolerated dose and the recommended phase 2 dose, pharmacokinetics, and preliminary efficacy.
Most of all treated patients (72.2%) had NSCLC. Additionally, 23.6% had colorectal cancer, and 4.2% had pancreatic ductal adenocarcinoma.
An ongoing phase 1/2 trial (NCT05002270) is also evaluating single-agent glecirasib in adult patients with advanced solid tumors harboring a KRAS G12C mutation.