Zynlonta: what was done before first-in-human, and what came after?

“The cynomolgus monkey was selected as nonclinical species for safety evaluation of loncastuximab tesirine, given the greater predictive value of PK data generated in this species for humans, potential for reduced impact of antidrug antibody (ADA) formation on drug exposure, and the proven utility of 1/6th highest non‐severely toxic dose (HNSTD) for setting clinical starting doses with ADCs.”

“The Applicant conducted GLP 4‐week and 13‐week repeat‐dose general toxicology studies in which cynomolgus monkeys were dosed with the ADC, followed by a 12‐week recovery period.”

“The Applicant conducted GLP 4‐week and 13‐week repeat‐dose general toxicology studies in which cynomolgus monkeys were dosed with the ADC, followed by a 12‐week recovery period.”

“Reproductive and developmental toxicology studies were not conducted since cytotoxic (i.e. genotoxic) drugs that affect actively dividing cells, such as loncastuximab tesirine, are expected to be embryo/feto toxic and teratogenic.”

“Reproductive and developmental toxicology studies were not conducted since cytotoxic (i.e. genotoxic) drugs that affect actively dividing cells, such as loncastuximab tesirine, are expected to be embryo/feto toxic and teratogenic.”

“Reproductive and developmental toxicology studies were not conducted since cytotoxic (i.e. genotoxic) drugs that affect actively dividing cells, such as loncastuximab tesirine, are expected to be embryo/feto toxic and teratogenic.”

“In accordance with ICH S9, ICH S6(R1) and ICH S1A (Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals) no carcinogenicity studies were conducted or are planned with ADCT-402 or SG3199 given the genotoxic mode of action of SG3199 (covalent DNA crosslinking/ alkylating agent) and the intended clinical use in patients with advanced cancer.”

“In accordance with ICH S9, ICH S6(R1) and ICH S1A (Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals) no carcinogenicity studies were conducted or are planned with ADCT-402 or SG3199 given the genotoxic mode of action of SG3199 (covalent DNA crosslinking/ alkylating agent) and the intended clinical use in patients with advanced cancer.”

“In accordance with ICH S9, ICH S6(R1) and ICH S1A, no carcinogenicity studies were conducted with loncastuximab tesirine or SG3199 given the genotoxic mode of action of SG3199 (see Section 5.5.2) and the intended clinical use in patients with advanced cancer.”