# Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers

Source: https://onco.cc/key-papers/paper-niche-2-nat-med-2020/  
OnCo record `paper-niche-2-nat-med-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the NICHE-2 trial registered as NCT03026140, in Nature Medicine (2020), chosen as the most cited paper whose own text cites the registry id.

## Summary

PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8 + PD-1 + T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.

Indexed on Europe PMC as PubMed record 32251400 (DOI 10.1038/s41591-020-0805-8). Its abstract cites the registry id NCT03026140, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature Medicine
- Year: 2020
- DOI: 10.1038/s41591-020-0805-8
- Authors: Chalabi M, Fanchi LF, Dijkstra KK, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT03026140 with the most citations, so it is the natural first reading for anyone following the NICHE-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- Nat Med 2020: https://doi.org/10.1038/s41591-020-0805-8
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32251400/
- Europe PMC: https://europepmc.org/article/MED/32251400
- ClinicalTrials.gov NCT03026140: https://clinicaltrials.gov/study/NCT03026140

## Connected records

- trials: [NICHE-2](https://onco.cc/trials/niche-2/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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