{"entity":{"id":"niche-2","kind":"trial","name":"NICHE-2","aka":[],"tldr":"In NICHE-2, four weeks of immunotherapy before surgery wiped out most mismatch-repair-deficient colon cancers, and nobody had relapsed three years later.","summary":"Pathologic response in 98%, major pathologic response 95%, pathologic complete response 68% (NEJM 2024). Three-year disease-free survival 100% (ESMO 2024). No patient needed chemotherapy. NICHE-3 (nivolumab + relatlimab) and the ATOMIC adjuvant trial extend the evidence; organ-preservation trials in rectal cancer (AZUR-1) follow the same logic.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03026140","url":"https://clinicaltrials.gov/study/NCT03026140"},{"label":"NEJM 2024","url":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2400634"}],"tags":[],"related":[],"cancers":["colorectal","msi-high-colorectal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab","ipilimumab"],"companies":[],"institutions":["nki"],"pathways":[],"terms":["msi","neoadjuvant-adjuvant","pcr"],"trials":["nct05855200","foxtrot"],"people":["myriam-chalabi"],"bottlenecks":[],"keyPapers":["paper-le-mmr-deficiency-pd1-nejm-2015","paper-moreira-lynch-syndrome-identification-jama-2012","paper-niche-2-nat-med-2020"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03026140","phase":"2","setting":"Locally advanced (mostly stage III) dMMR colon cancer: 4 weeks of neoadjuvant nivolumab + one dose ipilimumab, then surgery","sponsor":"Netherlands Cancer Institute","result":"pCR 68%, major pathologic response 95%; 3-year DFS 100%.","started":"2017-03-29","startedType":"actual","yearReported":2022,"enrolled":115,"enrolledBasis":"registered","enrolledNote":"ClinicalTrials.gov lists an estimated 353 participants for the amended NICHE protocol, which is still recruiting to further cohorts; the NEJM 2024 NICHE-2 analysis enrolled 115 patients, 111 of them in the efficacy analysis.","outcomes":[{"endpoint":"Pathologic complete response","primary":true,"unit":"percent","arms":[{"name":"Neoadjuvant nivolumab + ipilimumab","n":111,"value":68}],"source":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2400634"},{"endpoint":"3-year disease-free survival","unit":"percent","arms":[{"name":"Neoadjuvant nivolumab + ipilimumab","n":111,"value":100}],"source":"https://www.annalsofoncology.org/article/S0923-7534(24)03843-2/fulltext"}],"replication":"Single-arm; the ATOMIC phase 3 (adjuvant atezolizumab) and NICHE-3 corroborate dMMR immunotherapy benefit in the curative setting, but no randomised neoadjuvant trial has yet reported."},"route":"/trials/niche-2/","neighbours":{"cancer":[{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"institution":[{"id":"nki","kind":"institution","name":"Netherlands Cancer Institute (NKI-AvL)","route":"/institutions/nki/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"trial":[{"id":"foxtrot","kind":"trial","name":"FOxTROT","route":"/trials/foxtrot/"},{"id":"nct05855200","kind":"trial","name":"Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer","route":"/trials/nct05855200/"}],"person":[{"id":"myriam-chalabi","kind":"person","name":"Myriam Chalabi","route":"/people/myriam-chalabi/"}],"paper":[{"id":"paper-moreira-lynch-syndrome-identification-jama-2012","kind":"paper","name":"Identification of Lynch syndrome among patients with colorectal cancer","route":"/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/"},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","route":"/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/"},{"id":"paper-niche-2-nat-med-2020","kind":"paper","name":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","route":"/key-papers/paper-niche-2-nat-med-2020/"},{"id":"paper-niche-2-nejm-2024","kind":"paper","name":"NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients","route":"/key-papers/paper-niche-2-nejm-2024/"}],"pairing":[{"id":"neoadjuvant-io-dmmr","kind":"pairing","name":"Neoadjuvant checkpoint inhibitor → surgery (or no surgery) in dMMR colorectal cancer","route":"/pairings/neoadjuvant-io-dmmr/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"surgery-roadmap","kind":"roadmap","name":"Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work","route":"/roadmaps/surgery-roadmap/"},{"id":"trial-modernisation-roadmap","kind":"roadmap","name":"Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on","route":"/roadmaps/trial-modernisation-roadmap/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}],"idea":[{"id":"idea-bio2-neoadjuvant-biomarker-engine","kind":"idea","name":"Use pre-surgery immunotherapy windows as the field's biomarker engine","route":"/ideas/idea-bio2-neoadjuvant-biomarker-engine/"}]}}