Comparative Review of Phase I Dose-Finding Designs for Drug Combination Trials

• Activity Number: 31 - Combination Therapy Dose-Finding in Oncology Drug Development
• Type: Topic Contributed
• Date/Time: Monday, August 3, 2020 : 10:00 AM to 11:50 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Heng Zhou* and Ruitao LIN
• Companies: Merck and The University of Texas MD Anderson Cancer Center
• Keywords: Drug combination; MTD; model-based design; model-assisted design

Abstract

Drug combinations have been widely studied in oncology clinical trials in order to achieve better treatment effect. There are several challenges remained for determining the MTD in drug combination trials, like the toxicity order is partially known in dose matrix and there may be multiple MTDs exist. In recent years, a bunch of novel phase I dose-finding designs have been proposed to improve the design efficiency as compared with the traditional algorithm-based designs, e.g., 2-dimentional 3+3 design. The model-based designs, including Copula, POCRM, EWOC and BLRM designs, have been widely used. The model-assisted designs have attracted popularity recently for that they can share the simplicity of algorithm-based designs and excellent operating characteristics of model-based designs. Notable model-assisted designs include BOIN and keyboard designs. In this talk, we will review the aforementioned designs for drug combination trials and compare the performance among these designs in terms accuracy, safety, and reliability. Software for implementing these designs will be introduced as well.