Evidence map›Paper›PMID 41385448›Full record

ArticleActa haematologica2025

Anexelekto (Axl)/Mer Inhibitor Tamnorzatinib in Patients with Relapsed/Refractory Acute Myeloid Leukaemia: Results from a Phase I (Monotherapy) and Phase II (Combination with Venetoclax) Clinical Study.

Margaret T Kasner, Nigel Courtenay-Luck, Courtney DiNardo, Sean M Post, Praneeth Baratam, George N Magrath, Takaaki Nakamura, Akifumi Fujii, Sergio Prados, Naoki Honda and 3 more

Registry-linked trialAbstract read
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In one paragraph

Article in Acta haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03176277 (A Phase I/II Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Efficacy of ONO-7475 in Patients With Acute Leukemias or Myelodysplastic Syndromes), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03176277 phase1 / phase2terminatednot on this map

A Phase I/II Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Efficacy of ONO-7475 in Patients With Acute Leukemias or Myelodysplastic Syndromes

TypeinterventionalSponsorOno Pharmaceutical Co., Ltd.Ran2017 to 2023Enrolled42ConditionsAcute Leukemia, Myelodysplastic SyndromesArmsONO-7475 3mg once daily, ONO-7475 6mg once daily, ONO-7475 10mg once daily, ONO-7475 6mg + Venetoclax (70-400mg)
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Margaret T KasnerDepartment of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA, margaret.kasner@jefferson.edu.
Nigel Courtenay-LuckOno Pharma UK Ltd., London, UK.
Courtney DiNardoDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sean M PostDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Praneeth BaratamDivision of Hematology and Oncology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
George N MagrathStorm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA.
Takaaki NakamuraOno Pharmaceutical Co., Ltd., Osaka, Japan.
Akifumi FujiiOno Pharmaceutical Co., Ltd., Osaka, Japan.
Sergio PradosOno Pharma USA, Inc., Cambridge, Massachusetts, USA.
Naoki HondaOno Pharmaceutical Co., Ltd., Osaka, Japan.
Mary McbrideOno Pharma UK Ltd., London, UK.
Paula Edwards-HolmesOno Pharma UK Ltd., London, UK.
Robert StuartDivision of Hematology and Oncology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionRelapsed/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.

methodsTamnorzatinib 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.

resultsTamnorzatinib 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.

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

Indexed as

Axl/Mer inhibitorRelapsed/refractory acute myeloid leukaemiaTamnorzatinibTyrosine kinase inhibitorsVenetoclax

Identifiers

PMID41385448
PMCPMC12795523

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.