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Adagrasib, an irreversible KRASG12C inhibitor, showed clinical efficacy without new safety signals in patients with previously treated, advanced KRASG12C-mutated non-small-cell lung cancer
A confirmed objective response was seen in 42.9% of patients with non-small-cell lung cancer (NSLCLC) treated with adagrasib, a KRASG12C inhibitor: results of a study presented during the American Society of Clinical Oncology meeting and simultaneously published on The New England Journal of Medicine showed clinical efficacy without new safety signals.
The KRISTAL-1 study involved 116 patients with KRASG12C-mutated NSCLC previously treated with both platinum-based chemotherapy and anti–PD 1 or anti-PD-L1 immunotherapy; patients were treated with adagrasib, a KRASG12C inhibitor that irreversibly and selectively binds KRASG12C, locking it in its inactive state and that has been shown to have an acceptable adverse-event profile in the phase 1–1b part of the KRYSTAL-1 phase 1–2 study. Adagrasib (600 mg orally twice daily) showed a confirmed objective response in 42.9% of the 112 patients with a measurable disease at baseline. The median duration of response was 8.5 months and the median progression-free survival was 6.5 months. At a median follow-up of 15.6 months, the median overall survival was 12.6 months and among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3%. There were treatment-related adverse events of grade 3 or higher in 44.8% of patients, that resulted in discontinuation of the drug in 6.9% of patients. Taken together, data showed that adagrasib led to durable clinical benefit in patients with previously treated, advanced KRASG12C-mutated NSCLC. «Adagrasib continues to be evaluated as monotherapy and in combination with other therapies in NSCLC and in other advanced solid cancers within the KRYSTAL-1 study. A phase 3 trial evaluating adagrasib as compared with docetaxel is enrolling patients with previously treated KRASG12C– mutated NSCLC with eligibility criteria similar to those for KRYSTAL-1 and a phase 2 trial is evaluating adagrasib alone and in combination with pembrolizumab as first-line treatment in patients with advanced KRASG12C– mutated NSCLC», authors conclude.