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David S. Ettinger, MD, FACP, FCCP


ASCO 2022: Adagrasib Under Study in Advanced KRAS G12C–Mutated NSCLC

By: Julia Fiederlein
Posted: Monday, June 6, 2022

Alexander I. Spira, MD, PhD, FACP, of the Virginia Cancer Specialists Research Institute, Fairfax, and colleagues conducted the multicohort phase I/II KRYSTAL-1 trial to evaluate adagrasib (MRTX849) as monotherapy and in combination regimens in patients with advanced KRAS G12C–mutated solid tumors. The first disclosure from all patients enrolled in phase II’s cohort A, which was presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9002), suggested treatment with this investigational KRAS G12C inhibitor was well tolerated with “promising” efficacy in non–small cell lung cancer (NSCLC). A phase III trial comparing adagrasib monotherapy with docetaxel in previously treated patients with KRAS G12C–mutant NSCLC is ongoing.

A total of 116 patients with KRAS G12C–mutated NSCLC who had a history of platinum-based chemotherapy and anti–PD-1/L1 therapy were orally administered 600 mg of adagrasib twice daily. Follow-up data were provided for a median of 12.5 months. The objective response rate was 42.9%, and the disease control rate was 79.5%; a total of 31 patients remain on treatment. The median durations of response, progression-free survival, and overall survival were 8.5, 6.5, and 12.6 months, respectively.

Treatment-related adverse events of any grade were reported in 97.4% of patients; a total of 6.9% of treatment-related adverse events led to discontinuation of treatment. Diarrhea (62.9%), nausea (62.1%), vomiting (47.4%), fatigue (40.5%), increased levels of alanine aminotransferase/aspartate aminotransferase (27.6%/25.0%), and increased levels of blood creatinine (25.9%) were among the most frequently reported treatment-related adverse events of any grade. The most commonly reported grade 3 or 4 treatment-related adverse events were increased levels of lipase (6.0%) and anemia (5.2%).

Disclosure: For full disclosures of the study authors, visit

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