Evidence map›Paper›PMID 39278994›Full record

Trial reportNature medicine2024

Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial.

Peter G M de Gooyer, Yara L Verschoor, Lauren D W van den Dungen, Sara Balduzzi, Hendrik A Marsman, Marnix H Geukes Foppen, Cecile Grootscholten, Simone Dokter, Anne G den Hartog, Wieke H M Verbeek and 10 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIMulticenter Study
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 2 registered trials, which are not on this map. Cited by 76 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 4 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.

NCT03026140 phase2recruitingnot on this map

Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (Amended Protocol of: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL)

TypeinterventionalSponsorThe Netherlands Cancer InstituteRan2017 to 2032Enrolled353ConditionsColon CarcinomaArmsNivolumab, Ipilimumab, Celecoxib 200mg, BMS-986253, BMS-986016
NCT06971107 not yet recruitingnot on this mapstarted 2025, after this paper: background citation

TKRCD-MSI Study: Current Microsatellite Stability Findings in Colon Cancer - Nationwide Experience From Turkey

TypeobservationalSponsorTurkish Society of Colon and Rectal SurgeryRan2025 to 2029Enrolled1,500ConditionsColon Adenocarcinoma, MSI Positive Colorectal Cancer, MSI Negative Colorectal Cancer
3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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  17. Updates of CSCO guidelines for colorectal cancer version 2026.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026
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16 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.

Peter G M de GooyerDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Yara L VerschoorDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0009-0005-7217-1460
Lauren D W van den DungenDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Sara BalduzziDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1205-1895
Hendrik A MarsmanDepartment of Surgery, OLVG, Amsterdam, The Netherlands.
Marnix H Geukes FoppenDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Cecile GrootscholtenDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Simone DokterDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Anne G den HartogDepartment of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Wieke H M VerbeekDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Karlijn WoensdregtDepartment of Surgery, St Jansdal Hospital, Harderwijk, The Netherlands.
Joris J van den BroekDepartment of Surgery, Dijklander Hospital, Hoorn, The Netherlands.
Steven J OosterlingDepartment of Surgical Oncology, Spaarne Gasthuis, Haarlem and Hoofddorp, The Netherlands.
Ton N SchumacherDepartment of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-0517-8804
Koert F D KuhlmannDepartment of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Regina G H Beets-TanDepartment of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
John B A G HaanenDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-5884-7704
Monique E van LeerdamDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-5719-3208
Jose G van den BergDepartment of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Myriam ChalabiDepartment of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. m.chalabi@nki.nl.ORCID http://orcid.org/0000-0002-8607-6174

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by a defective DNA mismatch repair system, resulting in hypermutated and highly immunogenic tumors. Although patients with dMMR CC have limited benefit from chemotherapy, these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses. Here, based on data from melanoma studies, we postulated a high efficacy and favorable toxicity profile of anti-PD-1 plus anti-LAG-3. In the NICHE-3 study, a total of 59 patients with locally advanced dMMR CC were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 57 of 59 (97%; 95% confidence interval (CI): 88-100%) patients, meeting the primary endpoint. Responses included 54 (92%; 95% CI: 81-97%) major pathologic responses (≤10% residual viable tumor) and 40 (68%; 95% CI: 54-79%) pathologic complete responses. With a median follow-up of 8 months (range, 2-19), one patient had recurrence of disease. The treatment displayed an acceptable safety profile, with all-grade and grade 3-4 immune-related adverse events (irAEs) occurring in 80% and 10% of patients, respectively. The most common irAEs were infusion-related reactions (29%), thyroid dysfunction (22%) and fatigue (20%). In conclusion, our results show that neoadjuvant nivolumab/relatlimab induces high rates of pathologic responses and that further investigation of this treatment in larger studies is warranted. These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140 .

Indexed as

Colonic NeoplasmsDNA Mismatch RepairNeoadjuvant TherapyNivolumabAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsFemaleHumansLymphocyte Activation Gene 3 ProteinMaleMiddle AgedAntibodies, Monoclonal, HumanizedLymphocyte Activation Gene 3 ProteinNivolumab

Identifiers

PMID39278994
PMCPMC11564102

What Socratic holds

Textmetadata
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.