Evidence map›Paper›PMID 39107131›Full record

Trial reportJournal for immunotherapy of cancer2024

Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden.

Michael Schenker, Mauricio Burotto, Martin Richardet, Tudor-Eliade Ciuleanu, Anthony Gonçalves, Neeltje Steeghs, Patrick Schoffski, Paolo A Ascierto, Michele Maio, Iwona Lugowska and 18 more

Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03668119 (A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination With Ipilimumab or Nivolumab Monotherapy in Participants With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden), which is not on this map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
–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.

NCT03668119 phase2completednot on this map

A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination With Ipilimumab or Nivolumab Monotherapy in Participants With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)

TypeinterventionalSponsorBristol-Myers SquibbRan2018 to 2023Enrolled212ConditionsPan TumorArmsNivolumab, Ipilimumab
3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Review
  7. Advances and challenges in glioblastoma immunotherapy: a meta-analysis of immune checkpoint inhibitors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  8. Review
  9. Rare, Yet Targetable: New Perspectives on Ampullary Carcinomas.International journal of molecular sciences · 2026
    Review
  10. Reversing T cell dysfunction in a novelFrontiers in immunology · 2026
    Article
  11. Observational
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. 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

28 authors.

Michael SchenkerSf Nectarie Oncology Center and University of Medicine and Pharmacy, Craiova, Romania.
Mauricio BurottoBradford Hill Clinical Research Center, Santiago, Chile.
Martin RichardetFundación Richardet Longo, Instituto Oncológico de Córdoba, Córdoba, Argentina.
Tudor-Eliade CiuleanuDepartment of Oncology, Oncology Institute Prof Dr Ion Chiricuta, Cluj-Napoca, Romania.
Anthony GonçalvesDepartment of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
Neeltje SteeghsDepartment of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Patrick SchoffskiDepartment of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
Paolo A AsciertoDepartment of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy.ORCID http://orcid.org/0000-0002-8322-475X
Michele MaioDepartment of Oncology, University of Siena and Center for Immuno-Oncology, Siena, Italy.
Iwona LugowskaDepartment of Early Phase Clinical Trials, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Lorena LupinacciHospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Alexandra LearyUniversité Paris-Saclay and Institut Gustave‑Roussy, Villejuif, France.
Jean-Pierre DelordDepartment of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole, Toulouse, France.
Julieta GrasselliCenter for Medical Education and Clinical Research (CEMIC) University Hospital, Buenos Aires, Argentina.
David S P TanDepartment of Haematology-Oncology, National University Cancer Institute, Singapore.
Jennifer FriedmannSegal Cancer Center, Jewish General Hospital, Montreal, Québec, Canada.
Jacqueline VukyKnight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
Marina TschaikaBristol Myers Squibb, Princeton, New Jersey, USA.
Somasekhar KonduruBristol Myers Squibb, Princeton, New Jersey, USA.
Sai Vikram VemulaBristol Myers Squibb, Princeton, New Jersey, USA.
Ruta SlepetisBristol Myers Squibb, Princeton, New Jersey, USA.
Georgia KolliaBristol Myers Squibb, Princeton, New Jersey, USA.
Misena PaciusBristol Myers Squibb, Princeton, New Jersey, USA.
Quyen DuongBristol Myers Squibb, Princeton, New Jersey, USA.
Ning HuangBristol Myers Squibb, Princeton, New Jersey, USA.
Parul DoshiBristol Myers Squibb, Princeton, New Jersey, USA.
Jonathan BadenBristol Myers Squibb, Princeton, New Jersey, USA.ORCID http://orcid.org/0000-0002-9423-8305
Massimo Di NicolaMedical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy massimo.dinicola@istitutotumori.mi.it.ORCID http://orcid.org/0000-0002-7689-5774

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCheckpoint inhibitor therapy has demonstrated overall survival benefit in multiple tumor types. Tumor mutational burden (TMB) is a predictive biomarker for response to immunotherapies. This study evaluated the efficacy of nivolumab+ipilimumab in multiple tumor types based on TMB status evaluated using either tumor tissue (tTMB) or circulating tumor DNA in the blood (bTMB). PATIENTS AND

methodsPatients with metastatic or unresectable solid tumors with high (≥10 mutations per megabase) tTMB (tTMB-H) and/or bTMB (bTMB-H) who were refractory to standard therapies were randomized 2:1 to receive nivolumab+ipilimumab or nivolumab monotherapy in an open-label, phase 2 study (CheckMate 848; NCT03668119). tTMB and bTMB were determined by the Foundation Medicine FoundationOne

resultsIn total, 201 patients refractory to standard therapies were randomized: 135 had tTMB-H and 125 had bTMB-H; 82 patients had dual tTMB-H/bTMB-H. In patients with tTMB-H, ORR was 38.6% (95% CI 28.4% to 49.6%) with nivolumab+ipilimumab and 29.8% (95% CI 17.3% to 44.9%) with nivolumab monotherapy. In patients with bTMB-H, ORR was 22.5% (95% CI 13.9% to 33.2%) with nivolumab+ipilimumab and 15.6% (95% CI 6.5% to 29.5%) with nivolumab monotherapy. Early and durable responses to treatment with nivolumab+ipilimumab were seen in patients with tTMB-H or bTMB-H. The safety profile of nivolumab+ipilimumab was manageable, with no new safety signals.

conclusionsPatients with metastatic or unresectable solid tumors with TMB-H, as determined by tissue biopsy or by blood sample when tissue biopsy is unavailable, who have no other treatment options, may benefit from nivolumab+ipilimumab. TRIAL REGISTRATION NUMBER: NCT03668119.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsIpilimumabNeoplasmsNivolumabAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedMutationNeoplasm MetastasisIpilimumabNivolumabBiomarkerCirculating tumor DNA - ctDNACombination therapyImmune Checkpoint InhibitorTumor mutation burden - TMB

Identifiers

PMID39107131
PMCPMC11308901

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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 Socratic graph.