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

“Gedatolisib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay and not clastogenic in a human lymphocyte chromosomal aberration assay. Gedatolisib was not genotoxic in the in vivo rat bone marrow micronucleus assay.”

“In accordance with ICH S9 on the Nonclinical Evaluation for Anticancer Pharmaceuticals, no carcinogenicity studies have been conducted with gedatolisib.”

“Fertility and early embryonic development studies are not required as gedatolisib is indicated for the treatment of patients with advanced cancer. In addition, embryo-fetal development studies were not conducted as gedatolisib will be administered in combination with palbociclib and fulvestrant, both of which are known to cause embryo-fetal developmental toxicities.”

“In a single dose safety pharmacology study, a 5 mg/kg IV dose of gedatolisib administered to dogs increased heart rate (24%) and arterial blood pressure (6%) compared to control 12- to 33-hours post-dose, without an effect on QTc prolongation or other ECG parameters.”