{"entity":{"id":"checkmate-816","kind":"trial","name":"CheckMate 816","aka":[],"tldr":"CheckMate 816 was the first trial to show that immunotherapy before lung cancer surgery improves survival.","summary":"CheckMate 816, trial NCT02998528 sponsored by Bristol Myers Squibb and reported in 2022, was the first trial to show that immunotherapy before lung cancer surgery improves survival. It randomised 358 patients with resectable stage IB to IIIA non-small-cell lung cancer to three cycles of nivolumab plus platinum chemotherapy or chemotherapy alone, met both primary endpoints of pathologic complete response and event-free survival, showed an overall survival benefit in a 2025 update, and produced the first neoadjuvant-only immunotherapy approval in 2022. OnCo links it to the pCR and perioperative terms, to Tina Cascone, Jonathan Spicer, Patrick M. Forde and Valerie W. Rusch, and its event-free survival benefit was reproduced by KEYNOTE-671, AEGEAN, CheckMate 77T and NEOTORCH. Whether adding an adjuvant phase after neoadjuvant treatment adds anything is the open question.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT02998528","url":"https://clinicaltrials.gov/study/NCT02998528"}],"tags":[],"related":[],"cancers":["nsclc","resectable-nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","pcr"],"trials":[],"people":["tina-cascone","jonathan-spicer","valerie-rusch","patrick-forde"],"bottlenecks":[],"keyPapers":["paper-checkmate-816-nejm-2022","paper-checkmate-816-n-engl-j-med-2025-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02998528","phase":"3","setting":"Resectable stage IB-IIIA NSCLC: neoadjuvant nivolumab + platinum chemotherapy (3 cycles) vs chemotherapy","sponsor":"BMS","result":"EFS HR 0.63; OS HR 0.72.","started":"2017-03-04","startedType":"actual","yearReported":2022,"enrolled":358,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 505 participants (actual) across all arms, including nivolumab plus ipilimumab; the NEJM 2022 primary analysis compared 179 patients randomised to nivolumab plus chemotherapy with 179 randomised to chemotherapy.","outcomes":[{"endpoint":"Pathologic complete response","primary":true,"unit":"%","arms":[{"name":"Nivolumab + chemotherapy","n":179,"value":24},{"name":"Chemotherapy","n":179,"value":2.2}],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202170"},{"endpoint":"Event-free survival","primary":true,"unit":"months","arms":[{"name":"Nivolumab + chemotherapy","value":31.6},{"name":"Chemotherapy","value":20.8}],"hr":0.63,"ci":[0.43,0.91],"p":"0.005","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202170"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Nivolumab + chemotherapy","value":65},{"name":"Chemotherapy","value":55}],"hr":0.72,"ci":[0.52,0.99],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502256"}],"replication":"Confirmed by the perioperative trials KEYNOTE-671, AEGEAN, CheckMate 77T, and NEOTORCH, which all reproduced the EFS benefit."},"route":"/trials/checkmate-816/","neighbours":{"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"resectable-nsclc","kind":"cancer","name":"Resectable stage I to III non-small-cell lung cancer","route":"/cancers/resectable-nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"term":[{"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/"}],"person":[{"id":"jonathan-spicer","kind":"person","name":"Jonathan Spicer","route":"/people/jonathan-spicer/"},{"id":"patrick-forde","kind":"person","name":"Patrick M. Forde","route":"/people/patrick-forde/"},{"id":"tina-cascone","kind":"person","name":"Tina Cascone","route":"/people/tina-cascone/"},{"id":"valerie-rusch","kind":"person","name":"Valerie W. Rusch","route":"/people/valerie-rusch/"}],"paper":[{"id":"paper-checkmate-816-nejm-2022","kind":"paper","name":"CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery","route":"/key-papers/paper-checkmate-816-nejm-2022/"},{"id":"paper-checkmate-816-n-engl-j-med-2025-update","kind":"paper","name":"Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer","route":"/key-papers/paper-checkmate-816-n-engl-j-med-2025-update/"}],"trial":[{"id":"nct04025879","kind":"trial","name":"A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer","route":"/trials/nct04025879/"},{"id":"nct03800134","kind":"trial","name":"A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer","route":"/trials/nct03800134/"},{"id":"keynote-091","kind":"trial","name":"KEYNOTE-091 (PEARLS)","route":"/trials/keynote-091/"}],"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/"}],"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/"}]}}