Evidence map›Paper›PMID 37934611›Full record

ArticleThe Journal of clinical investigation2024

Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation.

Magnus T Dillon, Jeane Guevara, Kabir Mohammed, Emmanuel C Patin, Simon A Smith, Emma Dean, Gemma N Jones, Sophie E Willis, Marcella Petrone, Carlos Silva and 21 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02223923 (A Phase I Study to Assess the Tolerability, Safety and Biological Effects of ATR Inhibitor), which is not on this map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
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.

NCT02223923 phase1unknown statusnot on this map

A Phase I Study to Assess the Tolerability, Safety and Biological Effects of ATR Inhibitor (AZD6738) as a Single Agent and in Combination With Palliative Radiation Therapy in Patients With Solid Tumours

TypeinterventionalSponsorRoyal Marsden NHS Foundation TrustRan2014 to 2025Enrolled87ConditionsSolid Tumour Refractory to Conventional TreatmentArmsAZD6738, Palliative radiotherapy
3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 39 citations in OpenAlex.

  1. Trial
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  4. Driver mutation profiling by next-generation sequencing predicts survival and recurrence after curative-intent resection for pancreatic ductal adenocarcinoma: a genomic cohort study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  14. ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026
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  18. Review
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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

31 authors at 6 institutions in 2 countries.

Magnus T DillonThe Institute of Cancer Research, London, United Kingdom.
Jeane GuevaraThe Royal Marsden NHS Foundation Trust, London, United Kingdom.
Kabir MohammedThe Royal Marsden NHS Foundation Trust, London, United Kingdom.
Emmanuel C PatinThe Institute of Cancer Research, London, United Kingdom.
Simon A SmithOncology R&D, AstraZeneca, Cambridge, United Kingdom.
Emma DeanOncology R&D, AstraZeneca, Cambridge, United Kingdom.
Gemma N JonesOncology R&D, AstraZeneca, Cambridge, United Kingdom.
Sophie E WillisOncology R&D, AstraZeneca, Cambridge, United Kingdom.
Marcella PetroneClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom.
Carlos SilvaClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom.
Khin ThwayThe Royal Marsden NHS Foundation Trust, London, United Kingdom.
Catey BunceThe Royal Marsden NHS Foundation Trust, London, United Kingdom.
Ioannis RoxanisThe Institute of Cancer Research, London, United Kingdom.
Pablo NenclaresThe Institute of Cancer Research, London, United Kingdom.
Anna WilkinsThe Institute of Cancer Research, London, United Kingdom.
Martin McLaughlinThe Institute of Cancer Research, London, United Kingdom.
Adoracion Jayme-LaicheUCL Cancer Institute and University College London Hospital NHS Foundation Trust, London, United Kingdom.
Sarah BenafifUCL Cancer Institute and University College London Hospital NHS Foundation Trust, London, United Kingdom.
Georgios NintosKing's College London, and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
Vineet KwatraKing's College London, and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
Lorna GroveThe Institute of Cancer Research, London, United Kingdom.
David MansfieldThe Institute of Cancer Research, London, United Kingdom.
Paula ProszekThe Institute of Cancer Research, London, United Kingdom.
Philip MartinOncology R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Luiza MooreOncology R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Karen E SwalesThe Institute of Cancer Research, London, United Kingdom.
Udai BanerjiThe Institute of Cancer Research, London, United Kingdom.
Mark P SaundersThe Christie NHS Foundation Trust, Manchester, United Kingdom.
James SpicerKing's College London, and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
Martin D ForsterUCL Cancer Institute and University College London Hospital NHS Foundation Trust, London, United Kingdom.
Kevin J HarringtonThe Institute of Cancer Research, London, United Kingdom.
Royal Marsden NHS Foundation Trust · GBAstraZeneca (United Kingdom) · GBInstitute of Cancer Research · GBSt Thomas' Hospital · GBUniversity College Hospital · GBThe Christie Hospital · GB

Funding

Cancer Research UK 17796Cancer Research UK 28724
6 · The paper itself

Abstract

BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I study of the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced solid tumors.METHODSThe primary objective was safety. Secondary objectives included assessment of antitumor responses and pharmacokinetic (PK) and pharmacodynamic (PD) studies. Sixty-seven patients received 20-240 mg ceralasertib BD continuously or intermittently (14 of a 28-day cycle).RESULTSIntermittent dosing was better tolerated than continuous, which was associated with dose-limiting hematological toxicity. The recommended phase 2 dose of ceralasertib was 160 mg twice daily for 2 weeks in a 4-weekly cycle. Modulation of target and increased DNA damage were identified in tumor and surrogate PD. There were 5 (8%) confirmed partial responses (PRs) (40-240 mg BD), 34 (52%) stable disease (SD), including 1 unconfirmed PR, and 27 (41%) progressive disease. Durable responses were seen in tumors with loss of AT-rich interactive domain-containing protein 1A (ARID1A) and DNA damage-response defects. Treatment-modulated tumor and systemic immune markers and responding tumors were more immune inflamed than nonresponding.CONCLUSIONCeralasertib monotherapy was tolerated at 160 mg BD intermittently and associated with antitumor activity.TRIAL REGISTRATIONClinicaltrials.gov: NCT02223923, EudraCT: 2013-003994-84.FUNDINGCancer Research UK, AstraZeneca, UK Department of Health (National Institute for Health Research), Rosetrees Trust, Experimental Cancer Medicine Centre.

Indexed as

MorpholinesNeoplasmsPyrimidinesSulfonamidesAtaxia Telangiectasia Mutated ProteinsGenomicsHumansIndolesInflammationAtaxia Telangiectasia Mutated ProteinsATR protein, humanceralasertibIndolesMorpholinesPyrimidinesSulfonamidesCancer immunotherapyDNA repairDrug therapyOncology

Identifiers

PMID37934611
PMCPMC10786692
OpenAlexW4388446614

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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.