Faculty, Staff and Student Publications

Language

English

Publication Date

12-12-2025

Journal

Acta Haematologica

DOI

10.1159/000549340

PMID

41385448

PMCID

PMC12795523

PubMedCentral® Posted Date

12-12-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Relapsed/refractory (R/R) acute myeloid leukaemia (AML) is a life-threatening haematological malignancy without effective treatments. Anexelekto (Axl) and Mer receptor tyrosine kinases have emerged as important therapeutic targets in AML for their crucial role in survival of AML cells. Tamnorzatinib (ONO-7475) is a potent and highly selective inhibitor of Axl/Mer. We report first-in-human study of tamnorzatinib (NCT03176277) in patients with R/R AML.

Methods: Tamnorzatinib was administered as monotherapy (n = 20) to determine an appropriate biological dose of tamnorzatinib and then in combination (n = 22) with venetoclax to evaluate safety and clinical efficacy.

Results: Tamnorzatinib was safe and well tolerated as monotherapy (3, 6, and 10 mg) and in combination (6 mg) with venetoclax. No dose-limiting toxicities were observed at any dose level. Near-maximal Axl/Mer inhibition was observed following 6 mg tamnorzatinib alone and in combination therapy. No complete remission (CR) with partial haematologic recovery was observed with combination therapy. However, decreased transfusion dependency was observed; in the venetoclax-resistant subgroup (n = 14), 1 (7.1%) patient achieved CR with incomplete haematologic recovery and 1 (7.1%) patient achieved morphologic leukaemia-free state.

Conclusion: Tamnorzatinib alone and in combination with venetoclax was safe and well tolerated but failed to induce robust clinical efficacy in R/R AML.

Keywords

Axl/Mer inhibitor, Tamnorzatinib, Relapsed/refractory acute myeloid leukaemia, Tyrosine kinase inhibitors, Venetoclax

Published Open-Access

yes

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