Evidence map›Paper›PMID 41270699›Full record

ArticleESMO open2025

First-in-human study of a thorium-227-labeled mesothelin-targeting antibody-chelator conjugate (MSLN-TTC), in patients with malignant mesothelioma and other solid tumors.

A Minchom, O Lindén, D G Knapen, R Hassan, F I Lin, K Jalkanen, V Subbiah, A Tafuri, D Ferreira, V Jardine and 5 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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

15 authors.

A MinchomDrug Development Unit, Royal Marsden/Institute of Cancer Research, Sutton, UK. Electronic address: Anna.Minchom@icr.ac.uk.
O LindénDepartment of Oncology, Lund University Hospital, Lund, Sweden.
D G KnapenDepartment of Medical Oncology, University Medical Center Groningen, the Netherlands.
R HassanThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
F I LinMolecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
K JalkanenHelsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
V SubbiahDepartment of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), University of Texas MD Anderson Cancer Center, Houston, USA.
A TafuriPharmaceuticals, Bayer AG, Berlin, Germany.
D FerreiraPharmaceuticals, Bayer Healthcare Pharmaceuticals, Inc., Whippany, USA.
V JardinePharmaceuticals, Bayer PLC, Reading, UK.
A CletonPharmaceuticals, Bayer AG, Berlin, Germany.
J PinkertPharmaceuticals, Bayer AG, Berlin, Germany.
F BladtPharmaceuticals, Bayer AG, Berlin, Germany.
H HennekesPharmaceuticals, Bayer AG, Berlin, Germany.
E F SmitDepartment of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionBAY 2287411 [

methodsMSLN-TTC was administered i.v. 1.5, 2.5, or 3.5 MBq of thorium-227 and with a total antibody dose of 10, 30, 50, or 150 mg every 6 weeks to 36 patients included in the intention-to-treat population. Adverse events, tumor response according to RECIST 1.1 and mRECIST criteria, and progression-free survival were determined. Tumor mesothelin expression was assessed retrospectively.

resultsIn dose escalation, 35 patients (30 with malignant pleural mesothelioma) received MSLN-TTC across three thorium-227 dose levels and four total antibody doses. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached due to treatment discontinuations following 45.7% of the patients developing neutralizing antibodies. The most common treatment-emergent adverse events of any grade were fatigue (10/36, 27.8%), decreased lymphocyte count (7/36, 19.4%), nausea (7/36, 19.4%), anemia (6/36, 16.7%), and infusion-related reaction (6/36, 16.7%). The disease control rate was 34.3%, including 12 stable diseases (12/36, 34.3%). No complete or partial responses were observed. The median progression-free survival was 70 days (95% confidence interval 29-161 days).

conclusionsMSLN-TTC showed good tolerability, but the maximum tolerated dose could not be determined due to discontinuations after antidrug antibody formation. Stable disease was observed in 12 out of 36 patients.

Indexed as

Antibodies, MonoclonalChelating AgentsImmunoconjugatesMesothelioma, MalignantThoriumAdultAgedFemaleGPI-Linked ProteinsHumansMaleMesothelinMiddle AgedAntibodies, MonoclonalChelating AgentsGPI-Linked ProteinsImmunoconjugatesMesothelinMSLN protein, humanThoriumThorium-227mesothelinmesotheliomaovarian cancertargeted alpha therapythorium-227

Identifiers

PMID41270699
PMCPMC12670091

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Registered trials

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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.