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

“Despite a transient positive chromosomal aberration result at precipitating concentrations in vitro, the overall evidence strongly indicates that tovorafenib lacks clinically relevant genotoxic potential, a conclusion reinforced by negative in vivo micronucleus testing.”

“Tovorafenib was not carcinogenic in the 6-month study in transgenic rasH2 mice that received oral doses up to 100 mg/kg/day.”

“In an embryo-fetal development study, once daily oral administration of tovorafenib to pregnant rats during the period of organogenesis from gestation days 7 through 17 at doses of 37.5, 75, and 150 mg/kg resulted in early resorptions and total litter loss at all doses.”

“Both evidenced a dose-dependent increase in HR due to tovorafenib treatment, QT shortening and increase in SAP and MAP.”