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

“Tazemetostat did not cause genetic damage in a standard battery of studies including a screening and pivotal bacterial reverse mutation (Ames) assay, an in vitro micronucleus assessment in human peripheral blood lymphocytes, and an in vivo micronucleus assessment in rats after oral administration.”

“Dedicated carcinogenicity studies were not conducted with tazemetostat and are not required to support the use of a drug intended to treat patients with advanced cancer; however, findings in the rodent studies demonstrate that the drug has clear carcinogenic potential”

“Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure”

“No changes from control animals occurred in QA interval, body temperature, PR, QRS, and QT intervals in tazemetostat treated animals.”

“Tazemetostat did not cause genetic damage in a standard battery of studies including a screening and pivotal bacterial reverse mutation (Ames) assay, an in vitro micronucleus assessment in human peripheral blood lymphocytes, and an in vivo micronucleus assessment in rats after oral administration.”

“Tazemetostat did not cause genetic damage in a standard battery of studies including a screening and pivotal bacterial reverse mutation (Ames) assay, an in vitro micronucleus assessment in human peripheral blood lymphocytes, and an in vivo micronucleus assessment in rats after oral administration.”

“Tazemetostat did not cause genetic damage in a standard battery of studies including a screening and pivotal bacterial reverse mutation (Ames) assay, an in vitro micronucleus assessment in human peripheral blood lymphocytes, and an in vivo micronucleus assessment in rats after oral administration.”

“Dedicated carcinogenicity studies were not conducted with tazemetostat, but T-LBL, MDS, AML, and B-ALL have been reported clinically and T-LBL occurred in juvenile and adult rats after ~9 or more weeks of tazemetostat”

“Dedicated carcinogenicity studies were not conducted with tazemetostat and are not required to support the use of a drug intended to treat patients with advanced cancer”

“Tazemetostat inhibited the hERG potassium current with values ranging from 11.4 to 18.1% at 10 ϞΝ, making the IC50 greater than 10 ϞΝ suggesting a low potential for interference of cardiac repolarization and low risk of QT prolongation in humans given tazemetostat.”