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Adagrasib has shown durable clinical activity in patients with advanced KRASG12C-mutant non-small cell lung cancer (NSCLC), according to updated results from the KRYSTAL-1 trial presented at the 2023 World Conference on Lung Cancer.1
Adagrasib provided a “promising clinical benefit” across patient subgroups, including in patients with central nervous system (CNS) metastases and in those with co-mutations, study presenter Shirish Gadgeel, MD, of the Henry Ford Cancer Institute in Detroit, Michigan, said in a statement.2
Dr Gadgeel presented updated data from 2 cohorts of the phase 1/2 KRYSTAL-1 trial (ClinicalTrials.gov Identifier: NCT03785249).1 The 132 patients had KRASG12C-mutant unresectable or metastatic NSCLC and received adagrasib at 600 mg twice per day.
At a median follow-up of 26.9 months, the median overall survival (OS) was 14.1 months. The 1-year OS rate was 52.8%, and the 2-year OS rate was 31.3%.
The median progression-free survival (PFS) was 6.9 months. The 1-year PFS rate was 35.0%, and the 2-year PFS rate was 13.9%. The objective response rate was 43%, and the median duration of response was 12.4 months.
Among patients with CNS metastasis at baseline, the median PFS was 6.9 months, and the median OS was 14.7 months.
Among patients with co-mutations in KEAP1, the median PFS was 4.1 months, and the median OS was 5.7 months. Among patients with co-mutations in STK11, the median PFS was 4.2 months, and the median OS was 9.2 months.
Among patients with co-mutations in CDKN2A , the median PFS was 8.4 months, and the median OS was 13.0 months. Among patients with co-mutations in TP53, the median PFS was 8.7 months, and the median OS was 18.7 months.
No new safety signals were observed, Dr Gadgeel said. Among 12 patients who had received adagrasib within 30 days of receiving immunotherapy, none had grade 3 or higher hepatotoxicity. Treatment-related adverse events in patients treated for at least 1 year appeared to suggest there may be no cumulative toxicity with adagrasib, Dr Gadgeel said.
“In conclusion, in this pooled analysis of previously treated KRASG12C-mutated non-small cell lung cancer patients, adagrasib demonstrated durable clinical benefit, with a median survival of 14.1 months and a 2-year survival of 32%,” Dr Gadgeel said in his presentation.
Disclosures: This research was supported by Mirati Therapeutics, Inc. Study authors’ disclosures were not provided, but 4 authors are employed by Mirati Therapeutics, Inc.
References
1. Gadgeel S, Janne PA, Spira AI, et al. KRYSTAL-1: Two-year follow-up of adagrasib (MRTX849) monotherapy in patients with advanced/metastatic KRASG12C-mutated NSCLC. Presented at WCLC 2023. September 9-12, 2023. Abstract MA06.04.
2. KRYSTAL-1 trial finds that adagrasib demonstrates durable clinical activity in patients with KRAS G12C mutations. News release. International Association for the Study of Lung Cancer. September 10, 2023.
This article originally appeared on Cancer Therapy Advisor
