Expansion Cohorts in Early Development of Anticancer Agents

Drug development and clinical research in oncology are being completely transformed by precision medicine, which involves 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 an efficacy assessment. Furthermore, phase 1 trials have also moved away from the enrolment 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 1 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. 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 1 or 2 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 being the result of a true effect of therapy. In addition, the predictive role of biomarkers cannot be ascertained in a definitive way without randomization to a control arm.

Join this webinar to learn about:

• The recent literature related to the use and design features of phase 1/2 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• The key points in the recent FDA draft guidance for industry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 1 trials with expansion cohorts, including early consideration of randomization and issues related to sample size calculation

Speakers

Elisabeth (Els) Coart, PhD, Senior Biostatistician, Director of Consulting Services, International Drug Development Institute (IDDI)

Elisabeth Coart is a consultant in the design of early to late-stage clinical trials in various therapeutic areas. She brings over 10 years of experience as a statistician for biotech and diagnostic industries with a special interest in biomarker validation and biomarker-based clinical trials. Elisabeth also has a strong background in applied biology and assay development.

Message Presenter

Everardo Saad, MD, Medical Director, International Drug Development Institute (IDDI)

Everardo Saad has over 15 years of experience in medical oncology and clinical trial designs. He graduated in Medicine and trained in Internal Medicine in Sao Paulo, and did his fellowship in Medical Oncology at the University of Texas M.D. Anderson Cancer Center, in Houston. After practising for several years, he shifted his professional career towards education and research in medical oncology, and has a special interest in clinical trial methodology, the assessment of endpoints, and the development of novel therapies for cancer patients.

Message Presenter