TY  - JOUR
AU  - Loges, Sonja
AU  - Heuser, Michael
AU  - Chromik, Jörg
AU  - Sutamtewagul, Grerk
AU  - Kapp-Schwoerer, Silke
AU  - Crugnola, Monica
AU  - Di Renzo, Nicola
AU  - Lemoli, Roberto
AU  - Mattei, Daniele
AU  - Fiedler, Walter
AU  - Alvarado-Valero, Yesid
AU  - Ben-Batalla, Isabel
AU  - Waizenegger, Jonas
AU  - Rieckmann, Lisa-Marie
AU  - Janning, Melanie
AU  - Collienne, Maike
AU  - Imbusch, Charles D
AU  - Beumer, Niklas
AU  - Micklem, David
AU  - H Nilsson, Linn
AU  - Madeleine, Noëlly
AU  - McCracken, Nigel
AU  - Oliva, Cristina
AU  - Gorcea-Carson, Claudia
AU  - Gjertsen, Bjørn T
TI  - Bemcentinib as monotherapy and in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy: a phase 1b/2a trial.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00608
SP  - 2846
PY  - 2025
N1  - #EA:A420#
AB  - 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.
KW  - Humans
KW  - Cytarabine: administration & dosage
KW  - Cytarabine: adverse effects
KW  - Cytarabine: therapeutic use
KW  - Cytarabine: pharmacokinetics
KW  - Leukemia, Myeloid, Acute: drug therapy
KW  - Male
KW  - Middle Aged
KW  - Female
KW  - Aged
KW  - Antineoplastic Combined Chemotherapy Protocols: adverse effects
KW  - Antineoplastic Combined Chemotherapy Protocols: therapeutic use
KW  - Antineoplastic Combined Chemotherapy Protocols: pharmacokinetics
KW  - Antineoplastic Combined Chemotherapy Protocols: administration & dosage
KW  - Adult
KW  - Axl Receptor Tyrosine Kinase
KW  - Maximum Tolerated Dose
KW  - Receptor Protein-Tyrosine Kinases: antagonists & inhibitors
KW  - Proto-Oncogene Proteins: antagonists & inhibitors
KW  - Cytarabine (NLM Chemicals)
KW  - Axl Receptor Tyrosine Kinase (NLM Chemicals)
KW  - AXL protein, human (NLM Chemicals)
KW  - Receptor Protein-Tyrosine Kinases (NLM Chemicals)
KW  - Proto-Oncogene Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40122885
DO  - DOI:10.1038/s41467-025-58179-6
UR  - https://inrepo02.dkfz.de/record/300110
ER  -