Strategies to reduce the use of non-human primates in the development of oncology therapeutics: CD3-bispecifics.

Abstract

Pharmaceutical companies, which are IQ DruSafe/3R-TPS members, explored novel ways to reduce reliance on non-human primate (NHP) use in nonclinical drug development. These companies conducted a survey on NHP use in toxicology studies during discovery and development of CD3-bispecific antibodies (BsAbs) for the treatment of cancer. The objectives of the survey were to collect data on and case study examples of both first-in-human (FIH)-enabling (≤1-month) and Phase II/III-enabling (3-month) NHP studies conducted with CD3-BsAbs. The survey addressed study design elements, e.g. number of dose groups, number of animals/dose group, recovery arms, etc. when a study is deemed warranted. Survey questions also focused on whether data from Phase II/III-enabling studies addressed patient risk that was not identified in FIH-enabling studies, and whether Phase II/III-enabling studies impacted regulatory decisions pertaining to clinical development. The survey findings enabled the development of a Weight of Evidence (WoE) approach to assess the utility of Phase II/III-enabling toxicity studies in understanding potential safety risks with CD3 BsAbs and informing later-stage molecule development. Both study design optimization and WoE approaches offer a path for reduced NHP use without compromising nonclinical safety assessment of CD3-BsAbs for oncology indications, as illustrated by several case examples.