News
Article
Glecirasib Improved Response Rates, Survival in Patients With Non-Small Cell Lung Cancer
Author(s):
Key Takeaways
- Glecirasib showed promising efficacy in KRASG12C-mutated NSCLC, achieving a 47.9% ORR and 8.2 months median PFS.
- The trial reported a high disease control rate of 86.3% and a median overall survival of 13.6 months.
Glecirasib is a potent oral inhibitor of KRASG12C.
Glecirasib (JAB-21822; Jacobio Pharmaceuticals Group Co., Ltd) showed promising clinical potential for patients with locally advanced or metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) in a phase 2b JAB-21822 trial (NCT05009329). The treatment met both primary end points of overall response rate (ORR) and progression-free survival (PFS).1
3D depiction of KRAS G12C mutation in non-small cell lung cancer | Image Credit: © Aiden - stock.adobe.com
In the US, lung cancer is the most prevalent cause of cancer-related fatalities and the third most common type of cancer overall. NSCLC makes up almost 87% of all lung cancer diagnoses; however, only 25% to 30% of patients will respond to treatment. KRAS mutations occur in up to 30% of all cases and are associated with increased resistance and poorer outcomes.2,3
Glecirasib (Jacobio, Beijing, PRC) is a potent, highly selective covalent oral inhibitor of KRASG12C being explored for treatment of NSCLC. In the multi-center, open, dose-escalation, and expanded phase 1/2 clinical study JAB-21822 trial, glecirasib was assessed as a monotherapy in a total of 119 patients with NSCLC harboring KRASG12C mutations (median age: 62 years; 79% male, 21% female). Among the participants, about 94.1% had received prior platinum-based therapy and immune checkpoint inhibitors. Glecirasib was administered at a dosage of 800 mg daily.4
The trial’s primary end points were PFS and ORR assessed by independent review committee (IRC), with secondary end points including duration of response (DOR), PFS, overall survival (OS), disease control rate (DCR), and safety.4
The IRC reported an ORR of 47.9% (56/117; 95% CI, 38.5%-57.3%) and a confirmed DCR of 86.3% (101/117; 95% CI, 78.7%-92%). The median OS was 13.6 months (95% CI, 10.9–NE), with a median PFS per IRC of 8.2 months (95% CI, 5.5–13.1). There was no median DOR reported (95% CI, 7.2–NE).4
Overall, treatment-related adverse events (TRAEs) of any grade were observed in 97.5% of subjects. The most common TRAEs [greater than or equal to 15%] were anemia (56.3%), blood bilirubin increased (48.7%), alanine aminotransferase increased (35.3%), aspartate aminotransferase increased (35.3%), hypertriglyceridemia (28.6%) and γ-Glutamyl transferase increased (15.1%). Grade 3 and 4 TRAEs were observed in 39.5% of patients, but there were no grade 5 TRAEs that occurred.4
Most patients were able to continue treatment, with only 5.0% discontinuing due to TRAEs. Compared to other FDA-approved KRASG12C inhibitors, gleciasib demonstrated lower rates of gastrointestinal adverse events, with nausea in 6.7% of patients, vomiting in 7.6%, and diarrhea in 3.4%, with only 1 reported case of grade 3 nausea.4
These findings highlight glecirasib’s potential as a promising treatment option for patients with KRASG12C-mutated NSCLC, demonstrating a favorable balance between efficacy and safety. Further clinical investigation and long-term follow-up will be essential to confirm these results and explore glecirasib in broader patient populations or in combination with other therapies.
