{"entity":{"id":"harmoni-2","kind":"trial","name":"HARMONi-2","aka":[],"tldr":"The first head-to-head trial in which a new drug beat Keytruda, in China; a survival benefit followed in 2026.","summary":"HARMONi-2, trial NCT05499390 sponsored by Akeso and reported in 2024, was the first head-to-head trial in which a new drug beat pembrolizumab, comparing the PD-1 by VEGF bispecific ivonescimab with pembrolizumab as first-line monotherapy for PD-L1-positive advanced non-small-cell lung cancer in China. It randomised 398 patients, met its primary progression-free survival endpoint by independent review with a substantial improvement, and in 2026 Akeso and Summit reported a statistically significant overall survival benefit. OnCo links it to PD-1 and VEGF as targets, to Michelle Xia, Qing Zhou and Caicun Zhou, and to HARMONi-A. It was a single-country trial and the global HARMONi-3 interim analysis did not reproduce the progression-free survival margin, so whether Western regulators accept the result rests on HARMONi-3 and HARMONi-7. Ivonescimab has its own page.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT05499390","url":"https://clinicaltrials.gov/study/NCT05499390"},{"label":"Summit press release (2026 OS)","url":"https://smmttx.com/news/press-releases/news-details/2026/Ivonescimab-Monotherapy-Demonstrates-Statistically-Significant-Overall-Survival-Benefit-Compared-to-Pembrolizumab-Monotherapy-in-PD-L1-Positive-Advanced-NSCLC-in-HARMONi-2-Study-Conducted-by-Akeso-in-China/default.aspx"}],"tags":[],"related":[],"cancers":["nsclc","pdl1-high-nsclc"],"sections":[],"technologies":["bispecific-antibody","checkpoint-inhibitor"],"targets":["pd1","vegf"],"drugs":["ivonescimab","pembrolizumab"],"companies":["akeso"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["xia-michelle","qing-zhou","zhou-caicun"],"bottlenecks":[],"keyPapers":["paper-harmoni-2-lancet-2025"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05499390","phase":"3","setting":"First-line PD-L1-positive (TPS ≥1%) advanced NSCLC in China: ivonescimab vs pembrolizumab monotherapy","sponsor":"Akeso","result":"PFS HR 0.51; OS statistically significant (2026 announcement).","started":"2022-11-09","startedType":"actual","yearReported":2024,"enrolled":398,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (IRRC)","primary":true,"unit":"months","arms":[{"name":"Ivonescimab","n":198,"value":11.1},{"name":"Pembrolizumab","n":200,"value":5.8}],"hr":0.51,"ci":[0.38,0.69],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02722-3/fulltext"}],"replication":"Single-country (China) trial; OS immature. The global HARMONi-3 interim did not reproduce the PFS margin, so replication outside China is unresolved."},"route":"/trials/harmoni-2/","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":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"ivonescimab","kind":"drug","name":"Ivonescimab","route":"/drugs/ivonescimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"akeso","kind":"company","name":"Akeso","route":"/companies/akeso/"}],"person":[{"id":"zhou-caicun","kind":"person","name":"Caicun Zhou","route":"/people/zhou-caicun/"},{"id":"xia-michelle","kind":"person","name":"Michelle Xia (Xia Yu)","route":"/people/xia-michelle/"},{"id":"qing-zhou","kind":"person","name":"Qing Zhou","route":"/people/qing-zhou/"}],"paper":[{"id":"paper-harmoni-2-lancet-2025","kind":"paper","name":"HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer","route":"/key-papers/paper-harmoni-2-lancet-2025/"}],"trial":[{"id":"harmoni-a","kind":"trial","name":"HARMONi-A","route":"/trials/harmoni-a/"}],"roadmap":[{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"}]}}