Tobias Polak

Chapter 3 54 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020* Number of initiated phase II trials Number of phase II trials Progression to phase III / success Ongoing Number of phase III trials Status AGENTS IN PHASE III TARGETS IN PHASE II A AGENTS IN PHASE II B C FDA-approved Mocetinostat Atezolizumab Tosedostat Temsirolimus Sirolimus Rigosertib Motixafortide Daratumumab AS1411 APR−246 Alisertib Nilotinib Ponatinib Selinexor Ruxolitinib Nivolumab Alvocidib Pembrolizumab Imatinib Talacotuzumab Pracinostat Oblimersen Sodium Volasertib Idasanutlin Ibrutinib Everolimus Devimistat Lestaurtinib Panobinostat Dasatinib Vorinostat Bortezomib Valspodar Uproleselan Ivosidenib Glasdegib Pevonedistat Enasidenib Quizartinib Lintuzumab Crenolanib Sorafenib Tipifarnib Gilteritinib Midostaurin Venetoclax GO 0 10 20 30 + 117 agents Target Other PD−(L)1 BCR−ABL FLT3 BCL2 CD33 No progression to phase III within one year / failed 0 5 10 15 Tagraxofusp Phase II trials preceding rst phase III trial 50 40 30 20 10 0 Belinostat Bemcentinib Figure 2: Targets and targeted agents in phase II and II clinical trials. A Overview of trials initiated each year from 2000 to September 2020. Top five targets, based on number of trials, are annotated in the bar plots. B Overview of top-50 targeted agents investigated in phase II clinical trials. In total, we observed 167 individual agents in phase II research for the treatment of AML between 2000 and September 2020. C Overview of targeted agents investigated in phase III clinical trials. Bars are annotated based on progression to phase III, phase III result and FDA approval. Furthermore, bars in phase II are annotated with the number of phase II trials initiated before the first phase III trial of that agent started. Position of FDA-approval indication depends on the pivotal trial on which approval was based. The primary target of each investigated agents is displayed. This implicates that the agents investigated in these trials may have been selected because of the expected benefit of modulation of targets other than the primary target of that agent (e.g., C-KIT inhibition by imatinib, of which the primary target is BCR-ABL). * Results are shown for January 2020 through September 2020.

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