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

“Capmatinib was not mutagenic in an in vitro bacterial reverse mutation assay and did not cause chromosomal aberrations in an in vitro chromosome aberration assay in human peripheral blood lymphocytes. Capmatinib was not clastogenic in an in vivo bone marrow micronucleus test in rats.”

“Carcinogenicity studies were not conducted for capmatinib or necessary for a drug intended for the treatment of patients with advanced cancer.”

“Oral administration of capmatinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations at maternal exposures less than the human exposure based on AUC at the 400 mg twice daily clinical dose ( see Data ).”

“Safety pharmacology studies with capmatinib indicated no significant effects on cardiac, CNS or respiratory functions. hERG IC50 is at 40 times the expected free drug Cmax (0.464 µM) at maximal therapeutic dose of 400 mg bid in humans.”