ABSTRACT:
Drug development and clinical research in oncology are being completely transformed by precision medicine, which entails the discovery of targeted drugs and their predictive biomarkers. The need to develop the drug/biomarker pair is leading to changes in the design of clinical trials in oncology. In particular, early clinical trials have evolved to incorporate efficacy assessment and phase I, which has also moved away from the enrollment of a large number of cancer types to a focused approach based on tumor biology and expected response to targeted agents or immunotherapy. One important change has been the advent of expansion cohorts in phase I trials, which have led to recent cases of conditional approval by regulatory agencies. Moreover, new guidance has been released by the US Food and Drug Administration (FDA) on this particular topic. Of note, by matching very specific agents to actionable genomic alterations, precision medicine questions the need for randomized trials in some cases, and some remarkably efficacious drugs have even been approved based on uncontrolled phase I or II trials. However, apparently improved outcomes in a single-arm early trial may also be due at least in part to the prognostic nature of the specific genomic alteration and to selection bias, rather than result from a true effect of therapy. Moreover, the predictive role of biomarkers cannot be ascertained in a definitive way without randomization to a control arm.
IN THIS WEBINAR, WE REVIEWED:
- The recent literature related to the use and design features of phase I/II trials and those with expansion cohorts
- The key points in the recent FDA draft guidance for industry
- The statistical caveats to have in mind when designing phase I trials with expansion cohorts, including early consideration of randomization and issues related to sample size calculation.
SPEAKERS:
