AMG 211

In a high tumor mutation burden line (MTB111), 12/17 spikes showed subclonal alterations in APCA896V, F1515C, Q1544* that were not present in the parent culture... PDCOs identified subclonal alterations at the single-organoid level and are an exciting tool to study tumor heterogeneity. The spikes presented less subclonal variants than the parent but were largely not clonal. Future implications of using heterogeneity data from single organoids in therapeutic decisions are warranted.

The biodistribution of TCEs was verified by positron emission tomography imaging of [89Zr]AMG211 (a carcinoembryonic antigen-targeting TCE) in patients. The final model simulations indicated that the number of immune synapses is similar (~55/tumor cell) between two distinct clinical stage B cell maturation antigen (BCMA)-targeting TCEs, PF-06863135 in an IgG format and AMG420 in a BiTE format, at their respective efficacious doses in multiple myeloma patients. This result demonstrates the applicability of the developed computational modeling framework to molecular design optimization and clinical benchmarking for TCEs, thus suggesting that this framework can be applied to other targets to provide a quantitative means to facilitate model-informed best-in-class TCE discovery and development.