A pragmatic adaptive enrichment design for selecting the right target population for cancer immunotherapies

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ID: 281587
2020
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Abstract
One of the challenges in the design of confirmatory trials is to deal with uncertainties regarding the optimal target population for a novel drug. Adaptive enrichment designs (AED) which allow for a data-driven selection of one or more pre-specified biomarker subpopulations at an interim analysis have been proposed in this setting but practical case studies of AEDs are still relatively rare. We present the design of an AED with a binary endpoint in the highly dynamic setting of cancer immunotherapy. The trial was initiated as a conventional trial in early triple-negative breast cancer but amended to an AED based on emerging data external to the trial suggesting that PD-L1 status could be a predictive biomarker. Operating characteristics are discussed including the concept of a minimal detectable difference, that is, the smallest observed treatment effect that would lead to a statistically significant result in at least one of the target populations at the interim or the final analysis, respectively, in the setting of AED.
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wolbers2020a Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Anh Nguyen Duc; Dominik Heinzmann; Claude Berge; Marcel Wolbers
Journal arXiv
Year 2020
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