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While the latter have shown success in the clinic, efficacy has been constrained by therapeutic resistance, limited tumor penetration, and suboptimal immune activation. Currently, the ADC development space also includes the development of tumor\u2010targeting monoclonal antibodies that carry dual\u2010payloads, incorporating both cytotoxic agents and, for example, immunostimulatory molecules that could synergize direct tumor cell killing with reprogramming of the tumor immune microenvironment (TME). The translational and clinical pharmacology development strategy for ADCs is complicated by the need to understand the mechanism of action (MoA), the pharmacokinetics, and the pharmacodynamics of the different components of the ADC, and this gets even more complicated when two payloads are in play. 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