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Association details:
Biomarker:KRAS Q99L
Cancer:Solid Tumor
Drug:Krazati (adagrasib) (KRAS G12C inhibitor)
Direction:Resistant
Evidence:
Evidence Level:
Resistant: D – Preclinical
Title:

KRAS secondary mutations that confer acquired resistance to KRAS G12C inhibitors, sotorasib and adagrasib, and overcoming strategies: insights from the in vitro experiments

Published date:
05/07/2021
Excerpt:
142 Ba/F3 clones resistant to either sotorasib or adagrasib, of which 124 (87%) harbored secondary KRAS mutations. There were 12 different secondary KRAS mutations. Y96D/S was resistant to both inhibitors. A combination of novel SOS1 inhibitor, BI-3406, and trametinib showed potent activity against this resistance. While G13D, R68M and A59S/T which were highly resistant to sotorasib remained sensitive to adagrasib, Q99L was resistant to adagrasib but sensitive to sotorasib.
DOI:
https://doi.org/10.1016/j.jtho.2021.04.015