A model-free phase I/II dose optimization design for immunotherapy trials.

Abstract

We present a model-free phase I/II clinical trial design, referred to as the UFO design, to optimize the dose of immunotherapy by jointly modeling toxicity, efficacy, and immune response outcomes. Instead of relying on complex parametric modeling approaches, we propose a model-free approach that uses the inherent correlations among different types of outcomes in immunotherapy and the constrained dose-outcome order to facilitate information sharing across different doses. This approach ensures the efficiency and transparency of the UFO design to be implemented in clinical practice. The UFO design is also extended to accommodate the delayed outcomes. It demonstrates favorable operating characteristics through simulation studies. The R Shniy app for simulation and trial implementation using the UFO design is also provided at iusccc.shinyapps.io/smartdesign.