Expansion Cohorts in Early Development of Anticancer Agents
February 21, 2019
Free Webinar on Expansion Cohorts in Early Development of Anticancer Agents
Join us for a free webinar on expansion cohorts in early development of anticancer agents and learn on the statistical caveats when designing phase I trials with expansion cohorts.
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.
KEY LEARNING OBJECTIVES
- 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- The key points in the recent FDA draft guidance for industry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 1 trials with expansion cohorts, including early consideration of randomization and issues related to sample size calculation
Elisabeth (Els) Coart, PhD: Senior Biostatistician and IDDI’s Director of Consulting Services.
- She is a consultant in design of clinical trials, from early to late stage in various therapeutic areas.
- Els brings over 10 years of experience as statistician for biotech and diagnostic industries with a special interest in biomarker validation and biomarker based clinical trials.
- She has a strong background in applied biology and assay development.
Everardo Saad, MD: Medical Director at the International Drug Development Institute (IDDI).
- He 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 practicing 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.
Clinical trialists, statisticians, medical oncologists, immunologists, physicians, regulators, and other professionals involved in the design, conduct and analysis of oncology trials and in the application of trial results into practice.