Phase 2 Study of Glecirasib Meets Primary End Point in KRAS G12C-Mutant NSCLC
A pivotal phase 2 study evaluating glecirasib for the treatment of KRAS G12C-mutated advanced non-small cell lung cancer met its primary end point with an encouraging overall response rate.
Yuankai Shi, MD, PhD
Glecirasib (JAB-21822), a covalent, highly selective, and orally bioavailable KRAS G12C inhibitor, led to promising overall response rate (ORR), progression-free survival (PFS), and clinical activity when used as a treatment for patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC), according to topline results from a pivotal phase 2 study (NCT05009329).1
These findings were presented by Yuankai Shi, MD, PhD, at the American Society of Clinical Oncology (ASCO) Plenary Series: April Session.
Specifically, the confirmed ORR with gleciasib was 47.9% (95% CI, 38.5%-57.3%), meeting the primary end point of the single-arm trial. Additionally, the median PFS per independent review committee (IRC) was 8.2 months (95% CI, 5.5-13.1), the confirmed disease control rate (DCR) was 86.3% (95% CI, 78.7%-92%) assessed by IRC, the median overall survival (OS) was 13.6 months (95% CI, 10.9-not evaluable [NE]), and the median duration of response (DOR) has not been reached (95% CI, 7.2-NE).
“This phase 2 study of gleciasib monotherapy has met the study's primary end point demonstrating promising efficacy in previously treated KRAS G12C-mutated non-small cell lung cancer patients. The confirmed ORR per IRC was 47.9%, the median PFS [was] 8.2 months, and the median OS was 13.6 months,” said Shi, Cancer Hospital, Chinese Academy of Medical Sciences, during the presentation.
KRAS G12C mutation in non-small cell lung cancer: © Aiden - stock.adobe.com
For safety, glecirasib was shown to be well-tolerated and had a manageable safety profile with low incidences of nausea (6.7%), vomiting (7.6%), and diarrhea (3.4%). Notably, only 1 case of grade 3 nausea was reported. The gastrointestinal profile of glecirasib was favorable compared with other KRAS G12C inhibitors.
Treatment-related adverse events (TRAEs) of any grade were seen in 97.5% of patients with the most common seen in 10% of patients or more being 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%). A total of 39.5% of patients experienced a grade 3 or 4 TRAE, and no grade 5 TRAEs were seen. Additionally, 5.0% patients discontinued treatment due to a TRAE.
About the Phase 2 Study of Glecirasib
This phase 2, single-arm study of glecirasib was conducted in China across 43 sites.2 Patients with locally advanced or metastatic KRAS G12C-mutated NSCLC were enrolled who were previously treated with platinum-based therapy and an immune checkpoint inhibitor (ICI). Patients must have been aged 18 years or older, have an ECOG performance status of 0 or 1, have at least one measurable lesion as defined by RECIST v1.1, and have no serious organ dysfunction in the screening stage.
The trial included 119 patients with NSCLC harboring a KRAS G12C mutation.1 Patients were enrolled and treated with glecirasib as a single agent at a dose of 800 mg daily for a median follow-up of 10.4 months. At the median follow-up, 34.2% of patients were still on treatment.
"The study provided 90% power to ensure that the lower limit of 95% confidence interval exceeds the benchmark objective response of 23%," added Shi.
Among those enrolled in the study, the median age was 62 years. A total of 79% of patients were male, 21% were female, and 80.7% had an ECOG performance status of 1. Patients had received 1 to 3 prior lines of therapy, and 112 of the 119 patients (94.1%) were previously treated with platinum-based therapy and an ICI.
The primary end point of the study is ORR assessed by IRC, and secondary end points objectives include DOR, PFS, OS, DCR, safety, tolerability, and pharmacokinetics.
