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

  • Heuser, Michael1
  • Palmisiano, Neil2
  • Mantzaris, Ioannis3
  • Mims, Alice4
  • DiNardo, Courtney5
  • Silverman, Lewis R.6
  • Wang, Eunice S.7
  • Fiedler, Walter8
  • Baldus, Claudia9
  • Schwind, Sebastian10
  • Pardee, Timothy11
  • Perl, Alexander E.12
  • Cai, Charles13
  • Kaulfuss, Stefan14
  • Lagkadinou, Eleni14
  • Rentzsch, Christine14
  • Wagner, Markus14
  • Wilkinson, Gary14
  • Wu, Bingyan13
  • Jeffers, Michael13
  • And 2 more
  • 1 Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School,
  • 2 Thomas Jefferson University,
  • 3 Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
  • 4 The Ohio State University Comprehensive Cancer Center,
  • 5 The University of Texas M.D. Anderson Cancer Center,
  • 6 Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai,
  • 7 Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY USA
  • 8 University Hospital Hamburg-Eppendorf,
  • 9 Charité University Hospital Berlin,
  • 10 University Hospital Leipzig,
  • 11 Comprehensive Cancer Center of Wake Forest Baptist Health,
  • 12 Perelman School of Medicine, Abramson Cancer Center of the University of Pennsylvania,
  • 13 Bayer HealthCare Pharmaceuticals, Inc.,
  • 14 Bayer AG,
  • 15 Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg,
Published Article
Springer Nature
Publication Date
Jul 30, 2020
DOI: 10.1038/s41375-020-0996-5
PMID: 32733012
PMCID: PMC7584476
PubMed Central


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.

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