Novel biomarker enrichment designs in oncology drug development

Cancer Diagnostics Conference & Expo

June 13-15, 2016 Rome, Italy

Deepak Parashar

University of Warwick, UK

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Oncology trials based on biomarker stratified designs are increasingly being used to establish the effectiveness of a new drug or targeted therapy in specific populations of interest. Targeted or enriched designs are a class of such stratified trial designs that aim to enrich the biomarker-positive sub-population. In this talk, I shall discuss novel enrichment designs that determine whether a drug has activity only in the target population or the general population in the disease area. The enrichment is an adaptation based on the Simon two-stage design for Phase II oncology trials with a tumor response endpoint for a cytotoxic interventional drug. The group-sequential nature of the design and interim analyses allow one to make go/no-go decisions i.e., whether to progress the agent to a confirmatory trial or not. Appropriately controlling the type I and type II error probabilities yield novel optimal designs that minimize the expected sample size for a range of operating characteristics. Illustrating the issue of multiple testing, I shall present alternative family wise error rates and individual hypothesis control in weak as well as strong sense. An important feature of these designs is that they also evaluate efficacy in the biomarker-negative sub-population, an issue that has been highlighted by the FDA in recent years. Our approach can be generalized to randomized controlled trials with survival endpoints, and provides a robust framework for adaptive enrichment in biomarker-based Phase II/III trial design.

Biography :

Email: D.Parashar@warwick.ac.uk