Evidence map›Paper›PMID 40168999›Full record

ArticleCell reports. Medicine2025

TIMEPOINT, a phase 1 study combining MTL-CEBPA with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumors.

Ruth Plummer, Mikael H Sodergren, Rose Hodgson, Bríd M Ryan, Nina Raulf, Joanna P Nicholls, Vikash Reebye, Jon Voutila, Laura Sinigaglia, Tim Meyer and 28 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04105335 (An Open Label Phase 1a/b Study of MTL-CEBPA in Combination With a PD-1 Inhibitor), which is not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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.

NCT04105335 phase1completednot on this map

An Open Label Phase 1a/b Study of MTL-CEBPA in Combination With a PD-1 Inhibitor (Pembrolizumab) in Adult Patients With Advanced Solid Tumours

TypeinterventionalSponsorMina Alpha LimitedRan2019 to 2025Enrolled50ConditionsSolid Tumor, AdultArmsMTL-CEBPA, Pembrolizumab
3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Review
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  9. RNA activation ofMolecular therapy. Nucleic acids · 2025
    Article
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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

38 authors.

Ruth PlummerThe Northern Centre for Cancer Care, Freeman Hospital, NE7 7DN Newcastle, UK.
Mikael H SodergrenDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK.
Rose HodgsonMiNA Therapeutics Ltd, W12 0BZ London, UK.
Bríd M RyanMiNA Therapeutics Ltd, W12 0BZ London, UK.
Nina RaulfMiNA Therapeutics Ltd, W12 0BZ London, UK.
Joanna P NichollsDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK; MiNA Therapeutics Ltd, W12 0BZ London, UK.
Vikash ReebyeDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK; MiNA Therapeutics Ltd, W12 0BZ London, UK.
Jon VoutilaMiNA Therapeutics Ltd, W12 0BZ London, UK.
Laura SinigagliaMiNA Therapeutics Ltd, W12 0BZ London, UK.
Tim MeyerResearch Department of Oncology, UCL Cancer Institute, University College London, WC1E 6DD London, UK.
David J PinatoDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK; Department of Translational Medicine (DIMET), Università Del Piemonte Orientale "A. Avogadro", Novara, Italy.
Debashis SarkerDepartment of Research Oncology, Guys Hospital, Kings College London, SE1 9RT London, UK.
Bristi BasuUniversity of Cambridge and Cambridge University Hospitals NHS Foundation Trust, CB2 0QQ Cambridge, UK.
Sarah BlagdenDepartment of Oncology, Oxford University, Churchill Hospital, OX3 7LE Oxford, UK.
Natalie CookUniversity of Manchester and The Christie NHS Foundation Trust, M20 4BX Manchester, UK.
Thomas R Jeffrey EvansThe Beatson West of Scotland Cancer Centre, University of Glasgow, G12 0YN Glasgow, UK.
Jeffrey YachninCentrum Kliniska Cancerstudier, Karolinska University Hospital, 17176 Stockholm, Sweden.
Cheng E CheeNational University Hospital, National University Cancer Institute Singapore, Singapore 11928, Singapore.
Daneng LiDepartment of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Anthony El-KhoueiryNorris Comprehensive Cancer Centre, Keck Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Maria DiabWinship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Kai-Wen HuangNational Taiwan University Hospital, Taipei, Taiwan.
Madhava PaiDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK.
Duncan SpaldingDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK.
Thomas TalbotDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK.
Marcus S NoelMedstar Georgetown University Hospital, Washington, DC 20007, USA.
Bridget KeenanUniversity of California San Francisco, San Francisco, CA 94143, USA.
Devalingam MahalingamRobert H Lurie Comprehensive Cancer Centre, Northwestern University, Chicago, IL 60611, USA.
Min-Sun SongBeckman Research Institute, City of Hope, CA, USA.
Mélanie GrossoVeracyte, Marseilles, France.
Denis ArnaudVeracyte, Marseilles, France.
Aurelie AugusteVeracyte, Marseilles, France.
Dimitris ZacharoulisDepartment of General Surgery, University Hospital of Larissa, Larissa, Greece.
Jan StorkholmDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK.
Iain McNeishDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK.
Robert HabibMiNA Therapeutics Ltd, W12 0BZ London, UK.
John J RossiBeckman Research Institute, City of Hope, CA, USA.
Nagy A HabibDepartment of Surgery & Cancer, Imperial College London, W12 0NN London, UK; MiNA Therapeutics Ltd, W12 0BZ London, UK. Electronic address: nagy.habib@imperial.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many patients with cancer do not benefit from currently approved immune checkpoint inhibitors (ICIs), suggesting that additional immunomodulation of the immunosuppressive tumor microenvironment (TME) is required. MTL-CCAAT enhancer-binding protein alpha (CEBPA) specifically upregulates the expression of the master myeloid transcription factor, CEBPA, relieving myeloid-driven immunosuppression. Here, we report the safety, tolerability, pharmacokinetics, and efficacy of MTL-CEBPA in combination with pembrolizumab in patients with advanced solid tumors that typically show ICI resistance. Multimodal exploratory analyses of paired patient biopsies demonstrate biological changes associated with the combination treatment of MTL-CEBPA and pembrolizumab, including increased infiltration of T cell and antigen-presenting cells supporting conversion from an immune-desert toward a more immune-inflamed TME. Patients with disease stabilization demonstrate reductions in immunosuppressive myeloid cells post treatment. Collectively, these data support a role for MTL-CEBPA in reducing immunosuppression in the TME. This study was registered at ClinicalTrials.gov (NCT04105335).

Indexed as

Antibodies, Monoclonal, HumanizedImmunomodulationNeoplasmsAdultAgedFemaleHumansImmune Checkpoint InhibitorsMaleMiddle AgedTumor MicroenvironmentAntibodies, Monoclonal, HumanizedImmune Checkpoint Inhibitorspembrolizumabbiomarkercancergene activationimmunosuppressionimmunotherapyresistancetumor microenvironment

Identifiers

PMID40168999
PMCPMC12047497

What OpenQuestion holds

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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.