{"entity":{"id":"orient-4","kind":"trial","name":"ORIENT-4","aka":["Sintilimab in relapsed NK/T-cell lymphoma","IBI308 in extranodal NK/T-cell lymphoma"],"tldr":"A PD-1 antibody given alone shrank the lymphoma in three out of four people whose NK/T-cell lymphoma had come back after asparaginase chemotherapy.","summary":"NK/T-cell lymphoma that relapses after an asparaginase-based regimen had no standard. Its tumour cells commonly express PD-L1, which is the reason PD-1 antibodies were tried. ORIENT-4 was a single-arm, multicentre phase 2 study in China that gave the PD-1 antibody sintilimab, 200 mg intravenously every three weeks for up to 24 months, to 28 patients enrolled between August 2017 and February 2018 who had failed at least one asparaginase-based regimen.\n\nTwenty-one of the 28 (75.0 per cent, 95 per cent confidence interval 55.1 to 89.3) had an objective response by the Lugano 2014 criteria. At a median follow-up of 30.4 months median overall survival had not been reached and two-year overall survival was 78.6 per cent. Most treatment-related adverse events were grade 1 or 2, the commonest a fall in the lymphocyte count; serious adverse events occurred in seven patients and none died of an adverse event.\n\nIt is one of the studies behind the statement on the entity page that PD-1 blockade has substantial activity in relapsed disease. It is small and uncontrolled.","status":"positive","asOf":"2026-11-03","links":[{"label":"ClinicalTrials.gov NCT03228836","url":"https://clinicaltrials.gov/study/NCT03228836"},{"label":"Signal Transduction and Targeted Therapy 2021","url":"https://doi.org/10.1038/s41392-021-00768-0"}],"tags":["lymphoma-evidence-entities"],"related":[],"cancers":["extranodal-nk-t-cell-lymphoma","peripheral-t-cell-lymphoma"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["sintilimab"],"companies":["innovent"],"institutions":[],"pathways":[],"terms":["orr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-orient-4-sintilimab-nk-t-cell-lymphoma-2021"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03228836","phase":"2","setting":"Relapsed or refractory extranodal NK/T-cell lymphoma after at least one asparaginase-based regimen: sintilimab 200 mg every three weeks for up to 24 months","sponsor":"Innovent Biologics (Suzhou) Co. Ltd.","result":"Objective response in 21 of 28 (75.0 per cent); two-year overall survival 78.6 per cent.","started":"2017-08-23","startedType":"actual","yearReported":2021,"enrolled":28,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response rate (Lugano 2014)","primary":true,"unit":"%","arms":[{"name":"Sintilimab","n":28,"value":75,"note":"95 per cent confidence interval 55.1 to 89.3"}],"source":"https://doi.org/10.1038/s41392-021-00768-0"},{"endpoint":"Overall survival at 24 months","unit":"%","arms":[{"name":"Sintilimab","n":28,"value":78.6}],"source":"https://doi.org/10.1038/s41392-021-00768-0"}],"replication":"Consistent with smaller reports of other PD-1 antibodies in relapsed NK/T-cell lymphoma; no randomised comparison exists."},"route":"/trials/orient-4/","neighbours":{"cancer":[{"id":"extranodal-nk-t-cell-lymphoma","kind":"cancer","name":"Extranodal NK/T-cell lymphoma","route":"/cancers/extranodal-nk-t-cell-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"}],"company":[{"id":"innovent","kind":"company","name":"Innovent Biologics","route":"/companies/innovent/"}],"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"paper":[{"id":"paper-orient-4-sintilimab-nk-t-cell-lymphoma-2021","kind":"paper","name":"Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4)","route":"/key-papers/paper-orient-4-sintilimab-nk-t-cell-lymphoma-2021/"}]}}