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

“Tucatinib did not induce mutations in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration test or the in vivo mouse bone marrow micronucleus assay at doses up to the high dose of 2000 mg/kg.”

“No carcinogenicity studies were conducted or warranted to support this NDA, as the proposed indication was for advanced cancer.”

“Tucatinib administered to pregnant dams caused teratogenicity in rabbits and embryo-fetal toxicity in rats.”

“Tucatinib had no adverse effect on ECG, respiration, or neurological behavior in safety pharmacology studies.”

“Tucatinib did not induce mutations in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration test or the in vivo mouse bone marrow micronucleus assay at doses up to the high dose of 2000 mg/kg.”

“Tucatinib did not induce mutations in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration test or the in vivo mouse bone marrow micronucleus assay at doses up to the high dose of 2000 mg/kg.”

“Tucatinib did not induce mutations in the bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro chromosome aberration test or the in vivo mouse bone marrow micronucleus assay at doses up to the high dose of 2000 mg/kg.”

“No carcinogenicity studies were conducted or warranted to support this NDA, as the proposed indication was for advanced cancer.”

“No carcinogenicity studies were conducted or warranted to support this NDA, as the proposed indication was for advanced cancer.”

“In terms of safety pharmacology, tucatinib appeared selective for the intended HER2 tyrosine kinase target, showed low potential for interaction with cardiovascular targets (hERG, Human Embryonic Kidney (HEK293) Cells) and showed no clinically relevant adverse effects in the in vivo CV safety study in monkey.”