Evidence map›Paper›PMID 39775043›Full record

Trial reportNature medicine2025

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Reinhard Dummer, Caroline Robert, Richard A Scolyer, Janis M Taube, Michael T Tetzlaff, Alexander M Menzies, Andrew Hill, Jean-Jacques Grob, David C Portnoy, Celeste Lebbe and 11 more

Registry-linked trialAbstract readAdaptive Clinical TrialClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04303169 (A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma), which is not on this map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing 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.

NCT04303169 phase1 / phase2completednot on this map

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02C

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2020 to 2025Enrolled146ConditionsMelanomaArmsPembrolizumab, Vibostolimab, Gebasaxturev, MK-4830, Favezelimab + Pembrolizumab
3 · Its place in the literature

Who cites it

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

  1. Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: a joint SITC and INMC effort.Annals of oncology : official journal of the European Society for Medical Oncology · 2026
    Guideline
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  11. Neoadjuvant therapy in skin cancer: current evidence and future perspectives.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2026
    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

21 authors.

Reinhard DummerUniversity Hospital Zurich, Zurich, Switzerland. reinhard.dummer@usz.ch.ORCID 0000-0002-2279-6906
Caroline RobertGustave Roussy and Paris-Saclay University, Paris, France.ORCID 0000-0002-9493-0238
Richard A ScolyerMelanoma Institute Australia, The University of Sydney; Faculty of Medicine and Health, The University of Sydney; Royal Prince Alfred Hospital and NSW Health Pathology; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-8991-0013
Janis M TaubeJohns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA.ORCID 0000-0002-8273-4395
Michael T TetzlaffUniversity of California, San Francisco, CA, USA.
Alexander M MenziesMelanoma Institute Australia, The University of Sydney; Faculty of Medicine and Health, The University of Sydney; and Mater and Royal North Shore Hospitals, Sydney, New South Wales, Australia.
Andrew HillTasman Health Care, Southport, Queensland, Australia.
Jean-Jacques GrobAix-Marseille University Hôpital de la Timone, Marseille, France.
David C PortnoyWest Cancer Center and Research Institute, Germantown, TN, USA.ORCID 0009-0000-1614-1383
Celeste LebbeUniversité Paris Cité, Dermato-Oncology and CIC Hôpital Saint-Louis AP-HP, Cancer Institute AP-HP Nord-Université Paris Cité, Paris, France.ORCID 0000-0002-5854-7290
Muhammad A KhattakFiona Stanley Hospital and Edith Cowan University, Perth, Western Australia, Australia.
Jonathan CohenSharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Gil Bar-SelaEmek Medical Center, Afula, Israel.
Inderjit MehmiAngeles Clinic and Research Institute, a Cedars-Sinai affiliate, Los Angeles, CA, USA.
Ronnie Shapira-FrommerElla Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.
Nicolas MeyerDermatology, Clinique Médipole Garonne, Toulouse, France.
Andrea L WebberMerck & Co. Inc., Rahway, NJ, USA.
Yixin RenMerck & Co. Inc., Rahway, NJ, USA.
Mizuho Fukunaga-KalabisMerck & Co. Inc., Rahway, NJ, USA.
Clemens KreplerMerck & Co. Inc., Rahway, NJ, USA.
Georgina V LongMelanoma Institute Australia, The University of Sydney; Faculty of Medicine and Health, The University of Sydney; and Mater and Royal North Shore Hospitals, Sydney, New South Wales, Australia.ORCID 0000-0001-8894-3545

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 (47%) patients, respectively. Safety was manageable. Treatment-related adverse events occurred in 24 of 26 patients (92%) with pembrolizumab plus vibostolimab, 21 of 25 (84%) with pembrolizumab plus gebasaxturev and 12 of 15 (80%) with pembrolizumab monotherapy; grade 3 or 4 treatment-related adverse events occurred in 2 (8%), 7 (28%) and 1 (7%) patient in each arm, respectively. No deaths due to adverse events occurred. Exploratory objective responses per RECIST v1.1 were observed in 13 (50%), 8 (32%) and 4 (27%) patients, in each arm, respectively. In a post hoc analysis, scores for tumor mutational burden and an 18-gene T cell-inflamed gene expression profile were generally higher in patients with major pathologic response. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 .

Indexed as

Antibodies, Monoclonal, HumanizedMelanomaNeoadjuvant TherapyOncolytic VirotherapyProgrammed Cell Death 1 ReceptorAdultAgedFemaleHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasm StagingOncolytic VirusesAntibodies, Monoclonal, HumanizedImmune Checkpoint InhibitorsPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID39775043
PMCPMC11750705

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.