Novel Early Phase Clinical Trial Design in Oncology

Abstract

The development of investigational medicinal products from pre-clinical package to product launch is a process that may be beset by pitfalls and expensive failures. The focus of this review is to provide an overview of how the conventional design of early phase oncology clinical trials has been modified with the advent of molecular profiling into treatment paradigms. We identify classical and alternative trial endpoints in an era of molecularly targeted agents and immunotherapy, and consider how personalised medicine has impacted on clinical trial design with reference to basket, umbrella and multi-arm expansion cohorts. Finally, we assess the impact of agile, adaptive and ‘intelligent’ trial design for patients, clinicians and trial centres, and how these challenges may be overcome to accelerate the approval of novel drugs for patient benefit.