Evidence map›Paper›PMID 41823504›Full record

ArticleCancer2026

A phase 1 study of berzosertib (M6620, VX-970) in combination with cisplatin and radiation in patients with locally advanced head and neck squamous cell carcinoma (ETCTN 9950).

Aarti Bhatia, Zhengjia Chen, Yuji Zhang, Justine Yang Bruce, Susanne Arnold, Varinder Kaur, Jonathan W Riess, Moon Fenton, Barbara Burtness, Nabil F Saba and 17 more

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

Article in Cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

27 authors.

Aarti BhatiaYale School of Medicine and Yale Cancer Center, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0002-0491-4454
Zhengjia ChenDivision of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois, USA.
Yuji ZhangUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Justine Yang BruceDivision of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Susanne ArnoldMarkey Cancer Center, Lexington, Kentucky, USA.
Varinder KaurUniversity of Virginia, Charlottesville, Virginia, USA.
Jonathan W RiessDivision of Hematology/Oncology, UC Davis Comprehensive Cancer Center, Davis, California, USA.
Moon FentonDivision of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Barbara BurtnessYale School of Medicine and Yale Cancer Center, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0003-4660-1859
Nabil F SabaDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.ORCID https://orcid.org/0000-0003-4972-1477
Harold TaraYale School of Medicine and Yale Cancer Center, New Haven, Connecticut, USA.
Conor E SteuerDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
Dong M ShinDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
Garrett WaspDartmouth Cancer Center, Lebanon, New Hampshire, USA.ORCID https://orcid.org/0000-0002-1224-717X
Thomas H DavisDartmouth Cancer Center, Lebanon, New Hampshire, USA.
Malini PatelRutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
John C SchmitzUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Priyanka BhatejaOhio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Virginia DiavolitsisOhio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Dan P ZandbergDivision of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-1002-8301
Darrion L MitchellOhio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Brian F KieselCancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
Charles KunosSylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA.
Steven D GoreDivision of Cancer Treatment and Diagnosis, Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.
Michael CarducciDepartment of Oncology, Johns Hopkins University School of Medicine and Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, Maryland, USA.
Jan H BeumerDivision of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-8978-9401
Taofeek K OwonikokoUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0002-7724-7728

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
The Johns Hopkins Translational Science Team for the ET-CTNUM1CA186691 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Michael A Carducci · 2014 to 2026
$21.9M
Phase I Molecular and Clinical Pharmacodynamic Trials ETCTNUM1CA186717 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI A. Dimitrios Colevas, Alexey V. Danilov · 2014 to 2026
$19.8M
NCI ET-CTN with Phase i Emphasis at UPCIUM1CA186690 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD, Farshid Dayyani · 2014 to 2026
$9.1M
The Chesapeake-Ohio Pharmacokinetics Core for The ETCTNU24CA247648 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Mitch A Phelps · 2020 to 2026
$3.6M
PITT-CAL ETCTN PK Resource LaboratoryU24CA247643 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TIMOTHY W SYNOLD, Raman Venkataramanan · 2020 to 2026
$3.6M
Cancer Pharmacokinetics Research SpecialistR50CA211241 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PARISE, ROBERT · 2016 to 2025
$1.8M
Developing and Testing an Interactive Visual Aid for Approaching Decision Making to Stop Cancer Treatment in Advanced CancerK08CA286746 · NCI · DARTMOUTH-HITCHCOCK CLINIC · PI Garrett T Wasp · 2024 to 2026
$772k
NCI NIH HHS K08 CA286746NCI NIH HHS P30 CA047904NCI NIH HHS R50 CA211241NCI NIH HHS R50CA211241NCI NIH HHS U24 CA247643NCI NIH HHS U24CA247643NCI NIH HHS U24 CA247648NCI NIH HHS UM1 CA186690NCI NIH HHS UM1CA186690NCI NIH HHS UM1 CA186691NCI NIH HHS UM1CA186691NCI NIH HHS UM1 CA186717
6 · The paper itself

Abstract

backgroundAtaxia telangiectasia Rad3-related (ATR) protein kinase regulates DNA damage response and is essential for tumor cell survival. Preclinically, ATR inhibition can sensitize tumor cells to radiation and chemotherapy. The authors conducted a phase 1 trial of berzosertib, a selective ATR inhibitor, in combination with definitive radiation and cisplatin in locally advanced head and neck squamous cell cancers (LA-HNSCC).

methodsLA-HNSCC patients received daily radiation (2 Gy per fraction to 70 Gy) and weekly intravenous (iv) cisplatin 40 mg/m

resultsForty-one of 43 enrolled patients were evaluable for safety and preliminary efficacy assessments. Four patients experienced dose-limiting toxicities (DLTs) in dose-escalation: grade 4 thrombocytopenia (1), grade 4 respiratory failure (1), grade 3 renal injury and hypoxia (1), and inability to receive 90% of the planned radiation dose (1). DL3 was the recommended phase 2 dose, and 15 patients were enrolled at this DL as an expansion cohort. Objective response rates (ORR) in patient cohorts treated with any amount of berzosertib; treated with at least 50% of planned treatment; and in the expansion cohort were 78.8% (26 of 33), 78.8% (26 of 33), and 63.6% (7 of 11), respectively, after excluding eight inevaluable patients without post-treatment imaging assessment.

conclusionsBerzosertib (200 mg/m

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsChemoradiotherapyCisplatinHead and Neck NeoplasmsIsoxazolesPyrazinesSquamous Cell Carcinoma of Head and NeckAdultAgedFemaleHumansMaleMaximum Tolerated DoseMiddle AgedberzosertibCisplatinIsoxazolesPyrazinesATRberzosertibhead and neck cancerpharmacokineticsradiationsafety

Identifiers

PMID41823504
PMCPMC12984462

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.