Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial

Sonja Loges; Michael Heuser; Jörg Chromik; Grerk Sutamtewagul; Silke Kapp-Schwoerer; Monica Crugnola; Nicola Di Renzo; Roberto Lemoli; Daniele Mattei; Walter Fiedler; Yesid Alvarado-Valero; Isabel Ben-Batalla; Jonas Waizenegger; Lisa-Marie Rieckmann; Melanie Janning; Maike Collienne; Charles D. Imbusch; Niklas Beumer; David Micklem; Linn H Nilsson; Noëlly Madeleine; Nigel McCracken; Cristina Oliva; Claudia Gorcea-Carson; Bjørn T. Gjertsen

doi:10.1038/s41467-025-58179-6

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Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial

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Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial

Sonja Loges, Michael Heuser, Jörg Chromik, Grerk Sutamtewagul, Silke Kapp-Schwoerer, Monica Crugnola, Nicola Di Renzo, Roberto Lemoli, Daniele Mattei, Walter Fiedler, …

Nature communications, Vol.16(1), 2846

03/23/2025

DOI: 10.1038/s41467-025-58179-6

PMCID: PMC11930985

PMID: 40122885

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Abstract

Beyond first line, the prognosis of relapsed/refractory (R/R) acute myeloid leukemia (AML) patients is poor with limited treatment options. Bemcentinib is an orally bioavailable, potent, highly selective inhibitor of AXL, a receptor tyrosine kinase associated with poor prognosis, chemotherapy resistance and decreased antitumor immune response. We report bemcentinib monotherapy and bemcentinib+low-dose cytarabine combination therapy arms from the completed BerGenBio-funded open-label Phase 1/2b trial NCT02488408 ( www.clinicaltrials.gov ), in patients unsuitable for intensive chemotherapy. The primary objective in the monotherapy arm was identification of maximum tolerated dose with secondary objectives to identify dose-limiting toxicities, safety and efficacy, and bemcentinib pharmacokinetic profile. In the combination arm, the primary objective was safety and tolerability, with efficacy and pharmacokinetics as secondary objectives. Safety and tolerability were based on standard clinical laboratory safety tests and Common Terminology Criteria for Adverse Events version 4. Bemcentinib monotherapy (32 R/R, 2 treatment-naïve AML and 2 myelodysplasia patients) was well-tolerated and a loading/maintenance dose of 400/200 mg was selected for combination treatment, comprising 30 R/R and 6 treatment-naïve AML patients. The most common grade 3/4 treatment-related adverse events were cytopenia, febrile neutropenia and asymptomatic QTcF prolongation, with no grade 5 events reported. In conclusion, bemcentinib+low-dose cytarabine was safe and well tolerated. Following first-line therapy, patients with relapsed or refractory acute myeloid leukaemia (AML) have limited therapeutic options. Here, the authors report a phase 1b/2a study investigating bemcentinib (AXL inhibitor) as monotherapy and in combination with low-dose cytarabine (LDAC) in patients with relapsed or refractory AML.

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Title: Subtitle: Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial
Creators: Sonja Loges - Heidelberg University
Michael Heuser - Medizinische Hochschule Hannover
Jörg Chromik - University Hospital Frankfurt
Grerk Sutamtewagul - University of Iowa Hospitals and Clinics
Silke Kapp-Schwoerer - University Hospital Ulm
Monica Crugnola - University of Parma
Nicola Di Renzo - Ospedale Vito Fazzi
Roberto Lemoli - University of Genoa
Daniele Mattei - Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo
Walter Fiedler - University Medical Center Hamburg-Eppendorf
Yesid Alvarado-Valero - The University of Texas MD Anderson Cancer Center
Isabel Ben-Batalla - German Cancer Research Center
Jonas Waizenegger - German Cancer Research Center
Lisa-Marie Rieckmann - German Cancer Research Center
Melanie Janning - German Cancer Research Center
Maike Collienne - German Cancer Research Center
Charles D. Imbusch - German Cancer Research Center
Niklas Beumer - Heidelberg University
David Micklem - BerGenBio
Linn H Nilsson - BerGenBio
Noëlly Madeleine - BerGenBio
Nigel McCracken - BerGenBio
Cristina Oliva - BerGenBio
Claudia Gorcea-Carson - BerGenBio
Bjørn T. Gjertsen - Haukeland University Hospital
Resource Type: Journal article
Publication Details: Nature communications, Vol.16(1), 2846
DOI: 10.1038/s41467-025-58179-6
PMID: 40122885
PMCID: PMC11930985
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: Nature Publishing Group UK
Grant note: Hector Fellow Academy: 758713 BerGenBioEuropean Union: 445549683, GRK 2727/1 InCheck Hector Stiftung IIDeutsche Forschungsgemeinschaft, S.L.
We thank all the patients, investigators, and study coordinators who participated in and supported this study. BerGenBio provided financial support for the study and participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. Abbas Shivji and Oliver Dewhirst, who are employees of Exploristics UK, provided help with the generation of figures and tables. Funding was received from the following grants: Grant Agreement No. 758713, European Union's Horizon 2020 research and innovation program, S.L.; Hector Stiftung II (no grant number available), S.L.; Project 445549683, GRK 2727/1 InCheck, Deutsche Forschungsgemeinschaft, S.L., I.B-B.
Language: English
Date published: 03/23/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984802409202771

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