Model-informed dose selection in early oncology drug development

Diplôme Thèse Model-informed dose selection in early oncology drug development eng 2019-01-25 author Xiong Wenyuan 815176 director Csajka Chantal 657943 director Girard Pascal Roland 60163 10.13097/archive-ouverte/unige:133935 urn:nbn:ch:unige-1339355 Sc. 5436 Drug developers in oncology indication has been struggling with a low probability of success for decades. In my thesis, we studied how to improve the clinical proof-of-concept success rate with quantitative dosing rationale. We reviewed the classical dose selection strategies and the emerging transition of mathematical model-informed optimization strategies in anti-cancer drug development. Then we presented two case studies: first-in-human dose selection of avelumab, a monoclonal antibody, and the recommended phase II dose determination of tepotinib, a small-molecule kinase inhibitor. It showed how quantitative tools informed the dose selection with precision, and streamlined the early drug development path by avoiding unnecessary dose steps. The accumulating clinical data also proved, in both cases, successful dose strategies. By integrating preclinical in-vitro/in-vivo and clinical data across multiple development stages, the quantitative frameworks interpret the accumulating knowledge with great synergy, showing a high potential of model-informed optimization strategy to improve efficiency in drug development. Dewey 615 31 Section des sciences pharmaceutiques 17 false 01923985-f54e-4390-8cc7-b50a12d37fcf Thesis Public Full.thesis.Wenyuan.Xiong.pdf 5185454 application/pdf Private 2021-03-23 e33281b5eea4e3b865dc4d6e9fbf3211c0046d3bb9e1945fba2b3a14f9a9864b openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Xiong, Wenyuan