{"entity":{"id":"rationale-306","kind":"trial","name":"RATIONALE-306","aka":[],"tldr":"RATIONALE-306 is the trial behind tislelizumab's US approval for squamous oesophageal cancer, with the biggest gains in PD-L1-positive tumours.","summary":"RATIONALE-306, trial NCT03783442 sponsored by BeOne, formerly BeiGene, and reported in 2022, is the trial behind tislelizumab's US approval for first-line advanced oesophageal squamous cell carcinoma, with the biggest gains in PD-L1-positive tumours. It randomised 649 patients to tislelizumab or placebo with platinum chemotherapy and met its primary overall survival endpoint in all patients, published in Lancet Oncology in 2023, with a larger effect in PD-L1-positive disease; the FDA approved it on 4 March 2025 restricted to PD-L1 tumour area positivity of one percent or more, and the EU approved it in 2024. OnCo links it to oesophageal cancer, PD-1 as a target and tislelizumab, and the result is consistent with KEYNOTE-590, CheckMate 648 and ESCORT-1st. Whether a fifth PD-1 antibody in this setting competes on price rather than data is the practical question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03783442","url":"https://clinicaltrials.gov/study/NCT03783442"}],"tags":[],"related":[],"cancers":["esophageal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["tislelizumab"],"companies":["beone"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03783442","phase":"3","setting":"First-line advanced oesophageal squamous cell carcinoma: tislelizumab + platinum chemotherapy vs placebo + chemotherapy","sponsor":"BeOne (BeiGene)","result":"OS 17.2 vs 10.6 months (HR 0.66); PD-L1 ≥1% OS 16.8 vs 9.6 months.","started":"2018-12-11","startedType":"actual","yearReported":2022,"enrolled":649,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, all patients","primary":true,"unit":"months","arms":[{"name":"Tislelizumab + chemotherapy","n":326,"value":17.2},{"name":"Placebo + chemotherapy","n":323,"value":10.6}],"hr":0.66,"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00108-0/abstract"},{"endpoint":"Overall survival, PD-L1 ≥1%","unit":"months","arms":[{"name":"Tislelizumab + chemotherapy","value":16.8},{"name":"Placebo + chemotherapy","value":9.6}],"source":"https://www.onclive.com/view/fda-approves-first-line-tislelizumab-plus-chemotherapy-for-unresectable-or-metastatic-escc"}],"replication":"Consistent with KEYNOTE-590, CheckMate 648, ESCORT-1st."},"route":"/trials/rationale-306/","neighbours":{"cancer":[{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"}],"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":"tislelizumab","kind":"drug","name":"Tislelizumab","route":"/drugs/tislelizumab/"}],"company":[{"id":"beone","kind":"company","name":"BeOne Medicines (formerly BeiGene)","route":"/companies/beone/"}]}}