The therapeutic window of antibody drug conjugates: A dogma in need of revision

Despite a prevailing dogma wherein antibody drug conjugates (ADCs) increase the maximum tolerated dose of potent cytotoxin payloads while lowering the minimum effective dose, mounting clinical evidence argues that the tolerated doses of ADCs are not significantly different from those of related small molecules. Nonetheless, when dosed at or near the maximum tolerated dose, certain ADCs demonstrate improved efficacy. Understanding the challenges and opportunities for this class of biotherapeutics will help improve the design of next-generation ADCs.