{"entity":{"id":"impassion131","kind":"trial","name":"IMpassion131","aka":[],"tldr":"IMpassion131 was the sister trial to the first immunotherapy success in breast cancer. It failed, and the approval it was meant to confirm was withdrawn.","summary":"IMpassion130 (nab-paclitaxel partner) had shown a PFS benefit in PD-L1-positive metastatic TNBC and won accelerated approval in 2019. IMpassion131 used conventional paclitaxel (which requires steroid premedication) and showed no PFS or OS benefit; OS trended worse in the atezolizumab arm. Roche withdrew the US TNBC indication in 2021. Pembrolizumab with chemotherapy (KEYNOTE-355) became the standard instead.\n\nLesson: the chemotherapy partner (steroid premedication, immunogenic cell death profile) and the PD-L1 assay (SP142 vs 22C3) can decide an immunotherapy trial; confirmatory trials must replicate the winning design.","status":"negative","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT03125902","url":"https://clinicaltrials.gov/study/NCT03125902"},{"label":"Annals of Oncology 2021","url":"https://www.annalsofoncology.org/article/S0923-7534(21)02073-7/fulltext"},{"label":"IMpassion131 primary results (Annals of Oncology 2021)","url":"https://doi.org/10.1016/j.annonc.2021.05.801"}],"tags":["failure","lesson:partner-and-biomarker"],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["atezolizumab","paclitaxel","pembrolizumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["cps","accelerated-approval"],"trials":["impassion130","keynote-355"],"people":[],"bottlenecks":[],"keyPapers":["paper-impassion131-ann-oncol-2021"],"journals":[],"dependsOn":[],"notes":["Primary results (Annals of Oncology 2021): 651 patients randomised 2 to 1 to atezolizumab or placebo with paclitaxel 90 mg/m2; 45 percent PD-L1-positive. Investigator-assessed progression-free survival in the PD-L1-positive population 6.0 versus 5.7 months (hazard ratio 0.82, p 0.20); final overall survival 22.1 versus 28.3 months (hazard ratio 1.11, 0.76 to 1.64). Three UK sites (Guy's, the Christie, Mount Vernon)."],"nct":"NCT03125902","phase":"3","setting":"First-line metastatic TNBC: atezolizumab + paclitaxel vs paclitaxel","sponsor":"Roche","result":"PFS HR 0.82 (not significant); OS trend unfavourable; US indication withdrawn 2021.","started":"2017-08-25","startedType":"actual","yearReported":2020,"enrolled":653,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, PD-L1+ (investigator)","primary":true,"unit":"months","arms":[{"name":"Atezolizumab + paclitaxel","n":191,"value":6,"note":"Not significant"},{"name":"Placebo + paclitaxel","n":101,"value":5.7}],"hr":0.82,"ci":[0.6,1.12],"p":"0.20","source":"https://www.annalsofoncology.org/article/S0923-7534(21)02012-3/fulltext"},{"endpoint":"Overall survival, PD-L1+","unit":"months","arms":[{"name":"Atezolizumab + paclitaxel","value":22.1,"note":"Numerically unfavourable"},{"name":"Placebo + paclitaxel","value":28.3}],"hr":1.11,"ci":[0.76,1.64],"source":"https://www.annalsofoncology.org/article/S0923-7534(21)02012-3/fulltext"}],"replication":"Failed to replicate IMpassion130; the discordance is attributed to the taxane partner (steroid premedication with paclitaxel) and chance."},"route":"/trials/impassion131/","neighbours":{"cancer":[{"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":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"accelerated-approval","kind":"term","name":"Accelerated approval","route":"/terms/accelerated-approval/"},{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"}],"trial":[{"id":"impassion130","kind":"trial","name":"IMpassion130","route":"/trials/impassion130/"},{"id":"keynote-355","kind":"trial","name":"KEYNOTE-355","route":"/trials/keynote-355/"}],"paper":[{"id":"paper-impassion131-ann-oncol-2021","kind":"paper","name":"Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer","route":"/key-papers/paper-impassion131-ann-oncol-2021/"}],"roadmap":[{"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/"},{"id":"idea-tr2-contribution-of-components-mandate","kind":"idea","name":"No accelerated approval for a combination without proof each part contributes","route":"/ideas/idea-tr2-contribution-of-components-mandate/"}]}}