Safety and efficacy of BAY1436032 in IDH1-mutant AML: phase I study results

Michael Heuser, Neil Palmisiano, Ioannis Mantzaris, Alice Mims, Courtney DiNardo, Lewis R. Silverman, Eunice S. Wang, Walter Fiedler, Claudia Baldus, Sebastian Schwind, Timothy Pardee, Alexander E. Perl, Charles Cai, Stefan Kaulfuss, Eleni Lagkadinou, Christine Rentzsch, Markus Wagner, Gary Wilkinson, Bingyan Wu, Michael JeffersIsabelle Genvresse, Alwin Krämer

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing. Most subjects experienced only partial target inhibition as indicated by plasma R-2HG levels. BAY1436032 was safe and a maximum tolerated dose was not identified. The median treatment duration for all subjects was 3.0 months (0.49–8.5). The overall response rate was 15% (4/27; 1 CRp, 1 PR, 2 MLFS), with responding subjects experiencing a median treatment duration of 6.0 months (3.9–8.5) and robust R-2HG decreases. Thirty percent (8/27) achieved SD, with a median treatment duration of 5.5 months (3.1–7.0). Degree of R-2HG inhibition and clinical benefit did not correlate with dose. Although BAY1436032 was safe and modestly effective as monotherapy, the low overall response rate and incomplete target inhibition achieved at even the highest dose tested do not support further clinical development of this investigational agent in AML.

Original languageEnglish (US)
Pages (from-to)2903-2913
Number of pages11
Issue number11
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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