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

“Taletrectinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay and additional mutagenicity tests. Taletrectinib was not clastogenic or aneugenic in the in vivo micronucleus study in rats in bone marrow and liver.”

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

“In animal reproduction studies, oral administration of taletrectinib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal mortalities and structural abnormalities at exposures that were below or equal to the human exposure based on AUC at the recommended dose”

“In vitro, taletrectinib inhibited hERG currents and hNav1.5 with IC50 values of 0.98 µM and 0.83 µM, respectively, indicating a potential effect on QT prolongation. However, in the telemetered monkey cardiovascular study, there were no effects on any electrocardiogram (ECG) parameters, including QTc at the highest non-severely toxic dose (HNSTD) of 100 mg/kg/day.”