{"entity":{"id":"keynote-355","kind":"trial","name":"KEYNOTE-355","aka":[],"tldr":"Established immunotherapy plus chemotherapy as first-line treatment for metastatic triple-negative breast cancer with PD-L1 expression.","summary":"KEYNOTE-355, trial NCT02819518 sponsored by Merck and published in the New England Journal of Medicine in 2022, established pembrolizumab plus chemotherapy as first-line treatment for metastatic triple-negative breast cancer with PD-L1 expression. It randomised 847 patients and met its primary progression-free and overall survival endpoints in tumours with a combined positive score of ten or more, with no benefit below that threshold, which defined the PD-L1 cut-off used today. OnCo links it to triple-negative breast cancer, pembrolizumab, the CPS term, the TNBC roadmap and IMpassion131. It is now being succeeded by ADC-based first-line regimens such as ASCENT-04, and whether chemotherapy remains part of first-line treatment at all is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT02819518","url":"https://clinicaltrials.gov/study/NCT02819518"},{"label":"KEYNOTE-355 progression-free survival (Lancet 2020)","url":"https://doi.org/10.1016/S0140-6736(20)32531-9"},{"label":"KEYNOTE-355 overall survival (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2202809"},{"label":"NICE TA801 (29 June 2022)","url":"https://www.nice.org.uk/guidance/ta801"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["cps"],"trials":["keynote-119","impassion130","ascent-04","tropion-breast05"],"people":[],"bottlenecks":[],"keyPapers":["paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023","paper-keynote-355-lancet-2020"],"journals":[],"dependsOn":[],"notes":["Design (Lancet 2020): 847 patients randomised 2 to 1 to pembrolizumab or placebo with nab-paclitaxel, paclitaxel or gemcitabine and carboplatin at 209 sites in 29 countries; the registry figure of 882 includes the 32-patient part 1 safety run-in. Progression-free survival in CPS 10 or more 9.7 versus 5.6 months (hazard ratio 0.65); final overall survival (NEJM 2022) 23.0 versus 16.1 months in CPS 10 or more (hazard ratio 0.73, p 0.0185), 17.6 versus 16.0 in CPS 1 or more (0.86, not significant) and 17.2 versus 15.5 overall (0.89, not tested). Grade 3 to 5 treatment-related adverse events 68.1 versus 66.9 percent.","UK access: NICE TA801 (29 June 2022) limits the regimen to CPS 10 or more with immune-cell staining below 1 percent, because atezolizumab with nab-paclitaxel (TA639) is commissioned for the immune-cell-positive group."],"nct":"NCT02819518","phase":"3","setting":"First-line metastatic TNBC: pembrolizumab + chemotherapy vs chemotherapy","sponsor":"Merck","result":"OS HR 0.73 in CPS ≥10.","started":"2016-07-27","startedType":"actual","yearReported":2020,"enrolled":882,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, PD-L1 CPS ≥10","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","n":220,"value":23},{"name":"Placebo + chemotherapy","n":103,"value":16.1}],"hr":0.73,"ci":[0.55,0.95],"p":"0.0185","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202809"},{"endpoint":"Progression-free survival, PD-L1 CPS ≥10","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","value":9.7},{"name":"Placebo + chemotherapy","value":5.6}],"hr":0.66,"ci":[0.5,0.88],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202809"},{"endpoint":"Overall survival, CPS ≥1","unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","value":17.6,"note":"Not significant"},{"name":"Placebo + chemotherapy","value":16}],"hr":0.86,"ci":[0.72,1.04],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202809"}],"replication":"Consistent direction with IMpassion130 (atezolizumab, PD-L1+); IMpassion131 was negative, so the PD-L1 CPS ≥10 population and the chemotherapy partner matter. Now being superseded by ADC + pembrolizumab (ASCENT-04)."},"route":"/trials/keynote-355/","neighbours":{"cancer":[{"id":"tnbc-immunomodulatory","kind":"cancer","name":"Immunomodulatory triple-negative breast cancer (IM)","route":"/cancers/tnbc-immunomodulatory/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"pd-l1-assay-discordance","kind":"term","name":"PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)","route":"/terms/pd-l1-assay-discordance/"},{"id":"pd-l1-cps-10-tnbc","kind":"term","name":"PD-L1 combined positive score 10 in triple-negative breast cancer","route":"/terms/pd-l1-cps-10-tnbc/"}],"trial":[{"id":"ascent-04","kind":"trial","name":"ASCENT-04 / KEYNOTE-D19","route":"/trials/ascent-04/"},{"id":"impassion130","kind":"trial","name":"IMpassion130","route":"/trials/impassion130/"},{"id":"impassion131","kind":"trial","name":"IMpassion131","route":"/trials/impassion131/"},{"id":"keynote-119","kind":"trial","name":"KEYNOTE-119","route":"/trials/keynote-119/"},{"id":"tropion-breast05","kind":"trial","name":"TROPION-Breast05","route":"/trials/tropion-breast05/"}],"paper":[{"id":"paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023","kind":"paper","name":"Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms","route":"/key-papers/paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023/"},{"id":"paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021","kind":"paper","name":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","route":"/key-papers/paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021/"},{"id":"paper-keynote-355-nejm-2022","kind":"paper","name":"KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer","route":"/key-papers/paper-keynote-355-nejm-2022/"},{"id":"paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","kind":"paper","name":"PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer","route":"/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/"},{"id":"paper-keynote-355-lancet-2020","kind":"paper","name":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial","route":"/key-papers/paper-keynote-355-lancet-2020/"}],"roadmap":[{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","route":"/roadmaps/tnbc-history/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"idea":[{"id":"idea-tnbc-pd-l1-assay-harmonisation","kind":"idea","name":"Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance","route":"/ideas/idea-tnbc-pd-l1-assay-harmonisation/"}]}}