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The KRYSTAL-1 study of adagrasib — a new trial for KRASG12C-mutated non-small-cell lung cancer

The development of covalent, allele-specific inhibitors of KRASG12C represents a major breakthrough in precision oncology. Herein we discuss recent data from the phase II KRYSTAL-1 trial of adagrasib in KRASG12C-mutated non-small-cell lung cancer (NSCLC). This trial showed responses in a subset of patients, including among those with brain metastases, and offers exploratory insights into potential biomarkers of response.

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Y.R.M-G. has received a Kristina M. Day Young Investigator Award from Conquer Cancer, the ASCO Foundation (endowed by C.M. Baum and C.A. Baum), and has received training through an institutional K30 grant from the NIH (CTSA UL1TR00457). P.L. receives support in part from the Damon Runyon Cancer Research Foundation, NIH NCI (grants 1R01CA23074501 and 1R01CA23026701A1), the Pershing Square Sohn Cancer Research Alliance and The Pew Charitable Trusts. This work is supported by the NIH/NCI Cancer Center Support Grant (P30 CA008748) to Memorial Sloan Kettering Cancer Center.

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Correspondence to Piro Lito.

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Y.R.M-G. has received support for travel, accommodation and expenses from AstraZeneca, honoraria from Virology Education and Projects in Knowledge (for a program funded by an educational grant from Amgen) and acknowledges associated institutional research support funded by Elucida Oncology, Endeavor Biomedicines, Hengrui USA/Jiangsu Hengrui Pharmaceuticals, Loxo Oncology at Eli Lilly, Luzsana Biotechnology and Taiho Oncology and royalties from Rutgers University Press and Wolters Kluwer. P.L. is listed as an inventor on patents filed by MSKCC on the treatment of cancers with BRAF or KRAS mutations. P.L. receives institutional research support funded by Amgen, Boehringer Ingelheim, Mirati, Revolution Medicines and Virtec Pharmaceuticals, consulting fees or honoraria from AmMax Bio, Black Diamond Therapeutics, Boehringer Ingelheim, Repare Therapeutics and Revolution Medicines and is a member of the scientific advisory board for Frontier Medicines.

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Murciano-Goroff, Y.R., Lito, P. The KRYSTAL-1 study of adagrasib — a new trial for KRASG12C-mutated non-small-cell lung cancer. Nat Rev Clin Oncol 19, 677–678 (2022).

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