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 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 and Bjørn T. Gjertsen
Additional contact information
Sonja Loges: University Medical Center Mannheim
Michael Heuser: Hannover Medical School
Jörg Chromik: University Hospital Frankfurt
Grerk Sutamtewagul: University of Iowa Hospitals and Clinics
Silke Kapp-Schwoerer: University Hospital of Ulm
Monica Crugnola: University of Parma
Nicola Renzo: Vito Fazzi Hospital
Roberto Lemoli: University of Genoa
Daniele Mattei: Azienda Sanitaria Ospedaliera (ASO) Santa Croce e Carle
Walter Fiedler: University Medical Center Hamburg-Eppendorf
Yesid Alvarado-Valero: The University of Texas M.D. Anderson Cancer Center
Isabel Ben-Batalla: University Medical Center Mannheim
Jonas Waizenegger: University Medical Center Mannheim
Lisa-Marie Rieckmann: University Medical Center Mannheim
Melanie Janning: University Medical Center Mannheim
Maike Collienne: University Medical Center Mannheim
Charles D. Imbusch: German Cancer Research Center (DKFZ)
Niklas Beumer: University Medical Center Mannheim
David Micklem: BerGenBio ASA
Linn H Nilsson: BerGenBio ASA
Noëlly Madeleine: BerGenBio ASA
Nigel McCracken: BerGenBio Ltd
Cristina Oliva: BerGenBio Ltd
Claudia Gorcea-Carson: BerGenBio Ltd
Bjørn T. Gjertsen: University of Bergen

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58179-6

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