Evidence map›Paper›PMID 40750587›Full record

ArticleNature communications2025

Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial.

Magnus T Dillon, Emmanuel C Patin, Kabir Mohammed, Jeane Guevara, Simon A Smith, Emma Dean, Heba Soliman, Pablo Nenclares, Motoko Ryugenji, Davina Northcote and 11 more

Abstract readClinical Trial, Phase I
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. 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

21 authors.

Magnus T DillonThe Institute of Cancer Research, London, UK. magnus.dillon@icr.ac.uk.ORCID http://orcid.org/0000-0001-5136-5227
Emmanuel C PatinThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0001-5390-5733
Kabir MohammedThe Royal Marsden NHS Foundation Trust, London, UK.
Jeane GuevaraThe Royal Marsden NHS Foundation Trust, London, UK.
Simon A SmithAstraZeneca, Cambridge, UK.ORCID http://orcid.org/0000-0002-3591-3016
Emma DeanAstraZeneca, Cambridge, UK.ORCID http://orcid.org/0000-0001-9956-257X
Heba SolimanThe Royal Marsden NHS Foundation Trust, London, UK.
Pablo NenclaresThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-1750-3179
Motoko RyugenjiThe Royal Marsden NHS Foundation Trust, London, UK.
Davina NorthcoteThe Royal Marsden NHS Foundation Trust, London, UK.
Neel ShahAstraZeneca, Cambridge, UK.
Lorna GroveThe Institute of Cancer Research, London, UK.
Christopher J LordThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-3226-0515
Stephen PettitThe Institute of Cancer Research, London, UK.
Matt TallThe Institute of Cancer Research, London, UK.
Karen E SwalesThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-6572-1293
Udai BanerjiThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0003-1503-3123
Alan A MelcherThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-2042-3380
Mark SaundersThe Christie NHS Foundation Trust, Manchester, UK.
Martin D ForsterUCL Cancer Institute and University College London Hospital NHS Foundation Trust, London, UK.
Kevin J HarringtonThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-6014-348X

Funding

Cancer Research UK (CRUK) C7224/A23275; CRUKD/14/007; UK C347/A18077; C309/A25144; CTRQQR-2021\100009DH | National Institute for Health Research (NIHR) NIHR202438
6 · The paper itself

Abstract

Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. In this study, we explore the combination of the ATR inhibitor, ceralasertib, and palliative radiotherapy, with primary endpoint the identification of maximum tolerated dose, and secondary endpoints the determination of adverse event causality, pharmacokinetics (PK) and anti-tumor activity. Twenty-seven patients were dosed in escalating dose cohorts from 20 to 80 mg twice daily (BD) with concomitant radiation, 20 Gy in 10 fractions or 30 Gy in 15 fractions. Patients were assessed for acute and late toxicities and response after therapy. A non-tolerated dose was not reached. Maximum administered dose was 80 mg BD ceralasertib over 3 weeks with 30 Gy in 15 fractions, at which 1/6 evaluable patients had dose-limiting toxicities (radiation dermatitis and mucositis). PK was comparable to monotherapy. Of 23 efficacy-evaluable participants, 2 (9%) had complete response (CR), 6 (26%) partial response (PR), 13 (57%) stable disease (SD) and 2 (9%) progressive disease (PD) as best response in irradiated tumors. Response was not clearly linked to genomic aberrations. Increased T and natural killer cell activation as observed in peripheral blood as treatment progressed.

Indexed as

Ataxia Telangiectasia Mutated ProteinsNeoplasmsPyrimidinesAdultAgedAged, 80 and overFemaleHumansIndolesMaleMaximum Tolerated DoseMiddle AgedMorpholinesRadiation-Sensitizing AgentsSulfonamidesTreatment OutcomeAtaxia Telangiectasia Mutated ProteinsATR protein, humanceralasertibIndolesMorpholinesPyrimidinesRadiation-Sensitizing AgentsSulfonamides

Identifiers

PMID40750587
PMCPMC12316918

What OpenQuestion holds

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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.