Evidence map›Paper›PMID 34301752›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021

Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.

Timothy A Yap, Matthew G Krebs, Sophie Postel-Vinay, Anthony El-Khouiery, Jean-Charles Soria, Juanita Lopez, Alienor Berges, S Y Amy Cheung, Itziar Irurzun-Arana, Andrew Goldwin and 10 more

Open access · bronzeAbstract readClinical Trial, Phase I
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 1% 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.

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

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.

  1. Pooled it
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  16. ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026
    Article
  17. Integrated approaches to sensitizing melanoma to radiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026
    Review
  18. Article
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26 more citing papers are in PubMed but not listed here.

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

20 authors at 6 institutions in 5 countries.

Timothy A YapRoyal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-2154-3309
Matthew G KrebsDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.ORCID 0000-0001-7540-3064
Sophie Postel-VinayATIP-Avenir Group, INSERM Unit U981, Institut Gustave Roussy and Université Paris Saclay, Université Paris-Sud, Faculté de Médicine, Le Kremlin Bicêtre, and Department of Drug Development, DITEP, Institut Gustave Roussy, Villejuif, France.ORCID 0000-0001-5562-1857
Anthony El-KhouieryUSC Norris Comprehensive Cancer Center, Los Angeles, California.
Jean-Charles SoriaATIP-Avenir Group, INSERM Unit U981, Institut Gustave Roussy and Université Paris Saclay, Université Paris-Sud, Faculté de Médicine, Le Kremlin Bicêtre, and Department of Drug Development, DITEP, Institut Gustave Roussy, Villejuif, France.
Juanita LopezRoyal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom.
Alienor BergesQuantitative Clinical Pharmacology, AstraZeneca, Cambridge, United Kingdom.
S Y Amy CheungQuantitative Clinical Pharmacology, AstraZeneca, Cambridge, United Kingdom.
Itziar Irurzun-AranaQuantitative Clinical Pharmacology, AstraZeneca, Cambridge, United Kingdom.
Andrew GoldwinEarly Clinical Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Brunella FelicettiEarly Clinical Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Gemma N JonesTranslational Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Alan LauOncology Bioscience, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Paul FrewerOncology Biometrics, AstraZeneca, Cambridge, United Kingdom.
Andrew J PierceTranslational Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.ORCID 0000-0001-9062-0307
Glen ClackEarly Clinical Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Christine StephensEarly Clinical Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Simon A SmithEarly Clinical Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Emma DeanEarly Clinical Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Simon J HollingsworthOncology Business Unit, AstraZeneca, Cambridge, United Kingdom.
AstraZeneca (Singapore) · SGRoyal Marsden Hospital · GBUniversité Paris-Sud · FRAstraZeneca (United Kingdom) · GBManchester Academic Health Science Centre · GBUSC Norris Comprehensive Cancer Center · US

Funding

AstraZenecaChristieManchester Biomedical Research CentreManchester Experimental Cancer Medicine CentreNational Institute of Health ResearchNIHR Manchester Clinical Research Facility
6 · The paper itself

Abstract

purposeThis study reports the safety, tolerability, MTD, recommended phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of ceralasertib combined with carboplatin in patients with advanced solid tumors. It also examined exploratory predictive and pharmacodynamic biomarkers. PATIENTS AND

methodsEligible patients (n = 36) received a fixed dose of carboplatin (AUC5) with escalating doses of ceralasertib (20 mg twice daily to 60 mg once daily) in 21-day cycles. Sequential and concurrent combination dosing schedules were assessed.

resultsTwo ceralasertib MTD dose schedules, 20 mg twice daily on days 4-13 and 40 mg once daily on days 1-2, were tolerated with carboplatin AUC5; the latter was declared the RP2D. The most common treatment-emergent adverse events (Common Terminology Criteria for Adverse Events grade ≥3) were anemia (39%), thrombocytopenia (36%), and neutropenia (25%). Dose-limiting toxicities of grade 4 thrombocytopenia (n = 2; including one grade 4 platelet count decreased) and a combination of grade 4 thrombocytopenia and grade 3 neutropenia occurred in 3 patients. Ceralasertib was quickly absorbed (tmax ∼1 hour), with a terminal plasma half-life of 8-11 hours. Upregulation of pRAD50, indicative of ataxia telangiectasia mutated (ATM) activation, was observed in tumor biopsies during ceralasertib treatment. Two patients with absent or low ATM or SLFN11 protein expression achieved confirmed RECIST v1.1 partial responses. Eighteen of 34 (53%) response-evaluable patients had RECIST v1.1 stable disease.

conclusionsThe RP2D for ceralasertib plus carboplatin was established as ceralasertib 40 mg once daily on days 1-2 administered with carboplatin AUC5 every 3 weeks, with pharmacokinetic and pharmacodynamic studies confirming pharmacodynamic modulation and preliminary evidence of antitumor activity observed.

Indexed as

NeoplasmsNeutropeniaThrombocytopeniaAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsCarboplatinHumansIndolesMaximum Tolerated DoseMorpholinesNuclear ProteinsProtein Kinase InhibitorsPyrimidinesSulfonamidesSulfoxidesAtaxia Telangiectasia Mutated ProteinsATR protein, humanCarboplatinceralasertibIndolesMorpholinesNuclear ProteinsProtein Kinase InhibitorsPyrimidinesSLFN11 protein, humanSulfonamidesSulfoxides

Identifiers

PMID34301752
PMCPMC9401487
OpenAlexW3183394989

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.