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

“Repotrectinib was genotoxic in an in vitro assay in human lymphoblastoid TK6 cells and in an in vivo rat bone marrow micronucleus assay via an aneugenic mechanism of action. Repotrectinib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay.”

“Carcinogenicity studies have not been conducted with repotrectinib and are not warranted for the proposed indication.”

“In an embryo-fetal development study, once daily oral administration of repotrectinib to pregnant rats during the period of organogenesis from gestation day 6 to 17 resulted in maternal effects of increased body weight and skin abrasions/ulcerations at doses ≥6 mg/kg, fetal malformations of malrotated hindlimbs and lower fetal body weights at doses ≥12 mg/kg”

“Repotrectinib had no toxicologically significant effects on cardiovascular function in vivo in monkeys or in vitro on hERG, hNaV1.5, or hCaV1.2 channels. Repotrectinib had no effect on respiratory function rats and monkeys.”