OPTIM-ARTS—An Adaptive Phase II Open Platform Trial Design With Application to a Metastatic Melanoma Study

Abstract–Platform trials are increasingly popular in clinical research since these trials can evaluate multiple treatments in targeted subgroups of patients within a single trial infrastructure. In this article, we describe the development and implementation of a new clinical trial design OPTIM-ARTS (Open Platform Trial Investigating Multiple Compounds—Adaptive Randomized Design with Treatment Selection)—with application to a phase II study of an anti-PD-1 antibody in combination with other novel targeted therapies and immuno-agents in metastatic melanoma. The design consists of two main parts—the open platform (selection) phase, in which different treatments are initially assessed for efficacy in a randomized fashion, and the expansion phase, which will allow for a formal examination of efficacy with the selected promising treatment(s). The sample size for the expansion phase is chosen adaptively, using Bayesian shrinkage estimation, to mitigate selection bias due to potential random highs, and to ensure high predictive probability of obtaining significant final results. We performed calibration of the proposed design in a platform trial setting with four treatment arms and compared it with more standard designs. We found that our design is flexible and efficient, and it could be useful in an open platform trial setting with multiple investigational compounds.