Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer.

ABSTRACT:

Purpose

Patients with KRAS-mutant non-small cell lung cancer (NSCLC) with brain metastases (BM) have a poor prognosis. Adagrasib (MRTX849), a potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib has been optimized for favorable pharmacokinetic properties, including long half-life (∼24 hours), extensive tissue distribution, dose-dependent pharmacokinetics, and central nervous system penetration; however, BM-specific antitumor activity of KRASG12C inhibitors remains to be fully characterized.

Experimental design

A retrospective database query identified patients with KRAS-mutant NSCLC to understand their propensity to develop BM. Preclinical studies assessed physiochemical and pharmacokinetic pr

SUBMITTER: Sabari JK 

PROVIDER: S-EPMC9662862 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature