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

“Definitive genetic toxicology studies with belantamab mafodotin have not been conducted as it would be expected to be genotoxic based on its mechanism of action. Belantamab mafodotin was genotoxic in an in vitro micronucleus screening assay in human lymphocytes.”

“Belantamab mafodotin was genotoxic in an in vitro micronucleus screening assay in human lymphocytes. Genotoxicity assessments of cys-mcMMAF showed it was not mutagenic in the Ames test or genotoxic in the in vitro mouse lymphoma assay”

“The absence of carcinogenicity studies is accepted in line with the ICH S9 and S6(R1) guidelines.”

“The absence of carcinogenicity studies is accepted in line with the ICH S9 and S6(R1) guidelines.”

“Reproductive and developmental studies were not conducted since cytotoxic (i.e. genotoxic) drugs such as belantamab mafodotin which target rapidly dividing cells, are expected to be embryo/feto toxic and teratogenic. This position is consistent with the ICH S9 guidance.”

“Fertility studies have not been conducted with belantamab mafodotin. Results of repeat-dose toxicity studies with intravenous administration of belantamab mafodotin in rats indicate the potential for impaired male and female reproductive function and fertility.”

“Reproductive and developmental studies were not conducted since cytotoxic (i.e. genotoxic) drugs such as belantamab mafodotin which target rapidly dividing cells, are expected to be embryo/feto toxic and teratogenic. This position is consistent with the ICH S9 guidance.”

“No embryo-fetal or pre/ postnatal development studies have been conducted to support the development of belantamab mafodotin.”

“Reproductive and developmental studies were not conducted since cytotoxic (i.e. genotoxic) drugs such as belantamab mafodotin which target rapidly dividing cells, are expected to be embryo/feto toxic and teratogenic. This position is consistent with the ICH S9 guidance.”

“No stand-alone safety pharmacology studies were conducted, and safety pharmacology assessments were incorporated into the GLP-compliant general toxicology studies in Wistar Han rats and cynomolgus monkeys.”

“Genotoxicity assessments of cys-mcMMAF showed it was not mutagenic in the Ames test or genotoxic in the in vitro mouse lymphoma assay”

“In a non-GLP study, belantamab mafodotin was genotoxic in an in vitro micronucleus screening assay in human lymphocytes, with a statistically significant increase in the number of micronucleated binucleate cells that exceeded the laboratory control range.”

“Although cys-mcMMAF was not genotoxic in the rat bone marrow micronucleus assay, this is considered to reflect the low cell permeability of MMAF (due to its charged C terminal phenylalanine), because freely permeable MMAE was genotoxic in this assay”

“The absence of carcinogenicity studies is accepted in line with the ICH S9 and S6(R1) guidelines.”

“The absence of carcinogenicity studies is accepted in line with the ICH S9 and S6(R1) guidelines.”

“Cys-mcMMAF had no detectable effect on ionic currents in human embryonic kidney (HEK)293 cells stably expressing hERG channels at concentrations up to 100”