Antibody-drug conjugates as targeted therapies: Are we there yet? A critical review of the current clinical landscape

Abstract

Antibody-drug conjugates (ADCs) are targeted therapies with the expectation of broadened therapeutic window due to tumor-specific drug delivery. Recent approvals, including ADCs with a novel payload class, topoisomerase-1 inhibitors, generated renewed excitement in the field. We provide a critical review of approved and late-stage molecules, discuss strategies in solid tumors and ADCs outside oncology. Our pharmacokinetics-based assessment of targeting suggests that ADCs, especially in solid tumors, rely on additional mechanisms for efficacy including slow-release of the payload to the circulation at potentially efficacious levels. Further adjustments in the technology are needed to fulfill the promise of true targeted drug delivery.

Keywords: ADC; Antibody-drug conjugate; Exposure-response; PK; Pharmacokinetics; Prodrug; Slow-release; Targeted drug delivery.