Evidence map›Paper›PMID 38351187›Full record

Trial reportNature medicine2024

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M Forde, Maximilian J Hochmair, Mark M Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price and 28 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03334617 (An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy), which is not on this map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
30.5field-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.

NCT03334617 phase2active not recruitingnot on this map

An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON).

TypeinterventionalSponsorAstraZenecaRan2017 to 2026Enrolled528ConditionsNon-Small Cell Lung CancerArmsDurvalumab, Danvatirsen, Ceralasertib, Vistusertib, Olaparib
3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.

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  19. Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
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34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

38 authors at 20 institutions in 9 countries.

Benjamin BesseInstitut Gustave Roussy, Paris-Saclay University, Villejuif, France.ORCID 0000-0001-5090-8189
Elvire Pons-TostivintMedical Oncology, Centre Hospitalier Universitaire Nantes, Nantes University, Nantes, France.
Keunchil ParkSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Sylvia HartlLudwig Boltzmann Institute for Lung Health, Clinic Penzing, Vienna, Austria.ORCID 0000-0002-0734-0070
Patrick M FordeBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-6925-6344
Maximilian J HochmairDepartment of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria.
Mark M AwadDana-Farber Cancer Institute, Boston, MA, USA.
Michael ThomasDepartment of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Germany; Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Glenwood GossThe Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Paul Wheatley-PriceThe Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Frances A ShepherdDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Marie FlorescuDivision of Hematology Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Parneet CheemaWilliam Osler Health System, University of Toronto, Toronto, Ontario, Canada.
Quincy S C ChuCross Cancer Institute, Edmonton, Alberta, Canada.
Sang-We KimDepartment of Oncology, Asan Medical Center, Seoul, Republic of Korea.
Daniel MorgenszternDepartment of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Melissa L JohnsonSarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA.ORCID 0000-0001-9874-1314
Sophie CousinDepartment of Medical Oncology, Institut Bergonié, Regional Comprehensive Cancer Center, Bordeaux, France.
Dong-Wan KimSeoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.ORCID 0000-0001-5124-7132
Mor T MoskovitzInstitute of Oncology, Rambam Medical Center, Haifa, Israel.
David VicenteDepartment of Medical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain.
Boaz AronsonOncology Early Global Development, AstraZeneca, Gaithersburg, MD, USA.ORCID 0000-0001-8682-5190
Rosalind HobsonOncology Biometrics, AstraZeneca, Cambridge, UK.ORCID 0009-0003-7896-0490
Helen J AmbroseResearch and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK.
Sajan KhoslaReal-World Evidence, Oncology R&D, AstraZeneca, Cambridge, UK.
Avinash ReddyOncology Data Science, Oncology R&D, AstraZeneca, Boston, MA, USA.
Deanna L RussellTranslational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.ORCID 0000-0002-9650-2309
Mohamed Reda KeddarOncology Data Science, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK.
James P ConwayOncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.ORCID 0000-0002-1725-8193
J Carl BarrettTranslational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.
Emma DeanOncology R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0001-9956-257X
Rakesh KumarOncology R&D, AstraZeneca, Gaithersburg, MD, USA.ORCID 0000-0002-4627-3667
Marlene DressmanOncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Philip J JewsburyOncology R&D, AstraZeneca, Cambridge, UK.
Sonia IyerTranslational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.ORCID 0000-0003-3840-5583
Simon T BarryOncology R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-8511-0588
Jan CosaertOncology R&D, AstraZeneca, Cambridge, UK.
John V HeymachDepartment of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA. jheymach@mdanderson.org.ORCID 0000-0001-9068-8942
AstraZeneca (United Kingdom) · GBAstraZeneca (United States) · USThe University of Texas MD Anderson Cancer Center · USUniversity of Ottawa · CAAlberta Cancer Foundation · CAAsan Medical Center · KRBloomberg (United States) · USCentre Hospitalier de l’Université de Montréal · CACentre Hospitalier Universitaire de Nantes · FRDana-Farber Cancer Institute · USHeidelberg University · DEHospital Universitario Virgen Macarena · ESInstitut Bergonié · FRRabin Medical Center · ILSarah Cannon · USSeoul National University Hospital · KRSigmund Freud Privatuniversität Wien · ATUniversité Paris-Saclay · FRUniversity Health Network · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungIndolesLung NeoplasmsMorpholinesPyrimidinesSulfonamidesAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkersHumansPlatinumTumor MicroenvironmentAntibodies, MonoclonalAntineoplastic AgentsB7-H1 AntigenBiomarkersceralasertibdurvalumabIndolesMorpholinesPlatinumPyrimidinesSulfonamides

Identifiers

PMID38351187
PMCPMC10957481
OpenAlexW4391779877

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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.