Lazcluze: genotox, carcinogenicity and repro: done or skipped?

“Lazertinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay or clastogenic in either the in vitro chromosome aberration assay in Chinese hamster lung cells or the in vivo bone marrow micronucleus assay in rats.”

“The Applicant did not conduct carcinogenicity studies to support the currently proposed indication (NSCLC), and these studies are not needed to support a marketing application for a drug intended to treat patients with advanced cancer.”

“There was an increase in the incidence of skeletal malformations in the vertebra and skull (fused maxillary process/zygomatic arch), and unossified hyoid skull (skeletal variation) at 45 mg/kg compared to controls.”

“The unbound Cmax of lazertinib at the recommended human dose of 240 mg calculated by the FDA nonclinical team is ~6 nM, thus the 5.3 μM IC50 for hERG channel inhibition corresponds to an ~883-fold multiple.”