Jemperli: which tox species, and why?

“dostarlimab (TSR‐042) bound to human and cynomolgus monkey PD‐1 with similar affinity (KD = 1.8 and 1.5 nM, respectively) but did not bind to mouse PD‐1, supporting the use of cynomolgus monkey as the single pharmacologically relevant species for toxicity assessment.”

“dostarlimab (TSR‐042) bound to human and cynomolgus monkey PD‐1 with similar affinity (KD = 1.8 and 1.5 nM, respectively) but did not bind to mouse PD‐1”

“The Applicant evaluated the safety of dostarlimab in cynomolgus monkeys in GLP‐compliant repeat‐dose toxicity studies of up to 13 weeks duration.”

“dostarlimab (TSR‐042) bound to human and cynomolgus monkey PD‐1 with similar affinity (KD = 1.8 and 1.5 nM, respectively) but did not bind to mouse PD‐1, supporting the use of cynomolgus monkey as the single pharmacologically relevant species for toxicity”

“No reproductive and developmental studies were conducted because of potential adverse effects of the blockade of PD‐1/programmed death‐ligand 1 (PD‐L1) pathway on the immune tolerance at the fetomaternal interface. Consistent with the ICH S9 guidance, fertility assessments are not typically expected for products intended for the treatment of patients with cancer.”

“No genetic toxicology or carcinogenicity studies were conducted or warranted to support this BLA submission, as dostarlimab‐gxly is a biotechnology‐derived pharmaceutical and the proposed indication is for advanced cancer.”

“Because dostarlimab did not bind to mouse PD‐1, the Applicant developed a mouse surrogate anti‐PD‐1 antibody (RMP1‐14) to investigate the effects of PD‐1 pathway inhibition on tumor growth.”