All Times EDT
Keywords: Oncology, Dose Optimization, Therapeutic Index, Design
Dose-finding studies in oncology are largely performed only in Phase 1/1b clinical trials and intended to identify the maximum tolerated dose (MTD), a dose initially developed for systemic chemotherapies. With the emergence of novel targeted agents and immunotherapies, the notation that a higher dose will always lead to higher efficacy is no longer valid. Health authorities, such as the FDA are requiring more thorough dose finding and dose optimization prior to registrational studies, and encourage early interactions to discuss the dose optimization plan. The focus has turned towards identifying an optimal biological dose, determined based on the totality of safety, efficacy, pharmacokinetic and pharmacodynamic endpoints. Thoughtful study designs, translational data and modeling will play a more and more important role, tailed to the mechanism of action of the therapy and its therapeutic index. In this talk, a systematic overview will be provided on the strategic decision-making process, pragmatic statistical designs and considerations on dose optimization in oncology.