(E-196) Computational analysis of coadministration of antibody-drug conjugates to optimize payload delivery for solid tumor treatment

ADCs are efficacious cancer therapeutics that directly target cancer cells, concentrating damage within the tumor. Our previous work shows that coadministration of unconjugated antibody with its ADC, which competes for the same target sites, can improve distribution throughout the tumor and thus efficacy. Here we utilize SimADC, a hybrid agent-based model, to simulate a series of clinical payloads at a range of coadministration doses, to understand the conditions under which ADC efficacy can be improved. Our results indicate that dosing to reach all cells within the tumor results in the best possible efficacy, as reaching more cancer cells with ADC outweighs any decrease in killing of targeted cells provided there is at least some killing. Understanding the differences between these payload mechanisms can lead to greater efficacy for each type of drug and more personalized dosing regimens for cancer patients.