Ralston, Sherry, Li, Li1, Lee, Donna, Clark, Darcey, Dropsey, Andrew, Neff-LaFord, Haley, Rana, Payal, Weir, Lucinda, Sure, Radhakrishan and Waterhouse, Nathalie (2025) Strategies to reduce the use of NHP in development of oncology ADCs with cytotoxic payloads. Journal of Regulatory Toxicology and Pharmacology, 162 (105887). pp. 1-6. ISSN 2025.105887

Abstract

For the development of biologics and to a lesser extent small molecules, the use of non-human primates (NHP) for the nonclinical development of new drug candidates can be necessary to assess the potential safety risks in humans. As part of a collaborative effort through IQ DruSafe, a consortium of pharmaceutical companies is actively exploring ways to apply the 3Rs principles (Replacement, Refinement and Reduction) and reduce NHP use in nonclinical drug development while still ensuring patient safety of new potential therapeutic medicines. As one part of 3 workstreams to reduce NHP use in nonclinical safety testing, an IQ DruSafe Working Group (WG) conducted a survey on the use of NHP in toxicology studies used to develop antibody drug conjugates (ADCs) with cytotoxic payloads for the treatment of cancer. The objective of the survey was to understand whether a Good Laboratory Practice (GLP) compliant 3-month NHP study provides impactful additional safety information for ADCs with cytotoxic payloads relative to the 1-month GLP NHP or relative to the 3-month GLP rodent study (when conducted). The goal is to provide supporting evidence for potentially eliminating the 3-month NHP study if the data from the 3-month rodent study or 1-month NHP study is considered sufficient to inform potential safety risk in patients being administered ADCs with cytotoxic payloads. Questions from the survey included whether a 3-month NHP study was conducted and if so, were the results similar or not to those of the 3-month rodent study or the 1-month NHP study, if the toxicities observed were consistent with the expected toxicities of the ADC payload, and questions to address the translatability of the nonclinical findings to that observed in the clinic. In addition, survey questions addressed study design elements particularly related to the number of animals used on studies. The survey results indicated the following key points: for programs with 3-month studies in NHP and rodent, the target organ toxicities were generally similar between the studies and were translatable to humans; for programs with 3-month studies in NHP only, the target organ toxicities were generally similar between the 3-month and 1-month NHP studies and were translatable to humans. Target organ toxicities in both NHP and rodents were mostly attributed to the payload. Overall, survey results indicate an opportunity to reduce NHP use in the development of ADCs with cytotoxic payloads in oncology.

Item Type:	Article
Date Deposited:	16 Dec 2025 00:45
Last Modified:	16 Dec 2025 00:45
URI:	https://oak.novartis.com/id/eprint/56437