New clinical trial designs in the era of Precision Medicine

Abstract

Adaptive designs; Umbrella protocols; Basket protocols

Dissenys adaptatius; Protocols de paraigua; Protocols de cistell

Diseños adaptativos; Protocolos de paraguas; Protocolos de cesto

Cancer treatment has made significant strides towards the promise of personalized medicine. Recent scientific advances have shown that there are numerous genetic deregulations that are common in multiple cancer types, raising the possibility of developing drugs targeting those deregulations irrespective of the tumour type. Precision cancer medicine was born out of accumulated evidence matching targeted agents with these tumour molecular deregulations. At the same time, the therapeutic armamentarium is rapidly increasing and the number of new drugs (including immune-oncology agents) entering drug development continues to rise. These factors, added to strong collaboration with regulatory agencies which have approved novel agents based on data obtained from Phase 1/2 trials, have led to unprecedented evolution in the design of early stage clinical trials. Currently, we have seen rapid Phase 1 dose escalation trials followed by remarkably large expansion cohorts, and are witnessing the emergence of new trials, such as adaptive studies with basket and umbrella designs aimed at optimizing the biomarker-drug co-development process. Alongside the growing complexity of these clinical trials, new frameworks for stronger and faster collaboration between all stakeholders in drug development, including academic institutions and frameworks, clinicians, pharma companies and regulatory agencies, have been established. In this review article, we describe the main challenges and opportunities that these new trial designs may provide for a more efficient drug development process, which may ultimately help ensure that precision cancer medicine becomes a reality for patients