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Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS Mutation.
Pasi A Jänne1, Gregory J Riely1, Shirish M Gadgeel1
1From the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute (P.A.J.), and Massachusetts General Hospital (R.S.H.) - both in Boston; the Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College (G.J.R.), and Perlmutter Cancer Center, New York University Langone Health (J.K.S.), New York, and the Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo (E.Y.) - all in New York; the Henry Ford Cancer Institute, Detroit (S.M.G.); the University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange (S.-H.I.O.), the University of California San Diego Moores Cancer Center, La Jolla (L.B.), and Mirati Therapeutics, San Diego (K.A., H.D.-T., T.K., K.V., X.Y., J.G.C., R.C.C.) - all in California; the Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (J.M.P.); Sarah Cannon Research Institute at Tennessee Oncology, Nashville (M.L.J.); the Department of Oncology, Mayo Clinic, Rochester, MN (K.L.); the University of Texas M.D. Anderson Cancer Center, Houston (M.V.N.) and US Oncology Research, The Woodlands (A.I.S.) - both in Texas; Cleveland Clinic Taussig Cancer Institute, Cleveland (N.A.P.); the Division of Medical Oncology, Department of Internal Medicine, and the Department of Cancer Biology, University of Kansas Medical Center, Kansas City (J.Z.); and Virginia Cancer Specialists and NEXT Oncology Virginia - both in Fairfax (A.I.S.).
Adagrasib demonstrated clinical activity in patients with KRAS G12C-mutated non-small-cell lung cancer. This targeted therapy showed efficacy and an acceptable safety profile in previously treated individuals.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Adagrasib is a selective KRAS G12C inhibitor that targets the inactive state of the protein.
- Previous studies indicated adagrasib's clinical activity and safety in early-phase trials.
Purpose of the Study:
- To evaluate the efficacy and safety of adagrasib in patients with KRAS-mutated non-small-cell lung cancer (NSCLC).
- To assess objective response, duration of response, progression-free survival, overall survival, and safety in a registrational phase 2 cohort.
Main Methods:
- A phase 2 study evaluated adagrasib (600 mg orally twice daily) in patients with previously treated KRAS-mutated NSCLC.
- The primary endpoint was objective response rate assessed by blinded independent central review.
Main Results:
- Of 112 patients with measurable disease, 42.9% had a confirmed objective response.
- Median progression-free survival was 6.5 months, and median overall survival was 12.6 months.
- Treatment-related adverse events occurred in 97.4% of patients, with 44.8% experiencing grade 3 or higher events.
Conclusions:
- Adagrasib demonstrated clinical efficacy in patients with previously treated KRAS-mutated NSCLC.
- The safety profile was acceptable, with no new safety signals identified.
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