Ivonescimab lifted median survival to 30.8 months against pembrolizumab in HARMONi-2
A prespecified interim analysis of the phase 3 HARMONi-2 trial, presented at the World Conference on Lung Cancer in Seoul, put median overall survival at 30.8 months with ivonescimab against 22.6 months with pembrolizumab in 398 people in China with untreated PD-L1-positive advanced non-small cell lung cancer. The hazard ratio was 0.73. Akeso, the drug's developer, reads that as a 27 percent lower risk of death and says the gain was largest in PD-L1-high tumours. The safety profile stayed broadly comparable.
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Overall survival became the second endpoint HARMONi-2 met
The result was released on 13 September at the IASLC 2026 World Conference on Lung Cancer in Seoul, the annual meeting of the International Association for the Study of Lung Cancer. HARMONi-2 compares ivonescimab, a bispecific antibody developed by the Chinese biotechnology company Akeso that blocks both the PD-1 immune checkpoint and the blood-vessel growth signal VEGF, with pembrolizumab, the immunotherapy that has anchored first-line treatment of PD-L1-positive lung cancer. Between November 2022 and August 2023, 398 people at centres in China joined the trial, all with previously untreated locally advanced or metastatic non-small cell lung cancer, PD-L1 expression on at least 1 percent of tumour cells and no EGFR or ALK alterations; the two arms were split 1:1 between ivonescimab at 20 mg/kg and pembrolizumab at 200 mg every three weeks. At the 20 August 2026 data cutoff, after a median follow-up that Akeso puts at 36 months, 234 deaths had occurred. Median overall survival reached 30.8 months with ivonescimab against 22.6 months with pembrolizumab, a hazard ratio of 0.73 with a 95 percent confidence range of 0.57 to 0.95, which Akeso translates into a 27 percent reduction in the risk of death.[1], [2]
Squamous tumours and PD-L1-high patients showed the larger gains
The survival benefit was broadly consistent across prespecified subgroups, with the strongest signal where PD-L1 expression was highest. Among patients whose tumours expressed PD-L1 on at least 50 percent of cells, the hazard ratio was 0.58, with a range of 0.38 to 0.89; among those with expression between 1 percent and 49 percent it was 0.85, with a range of 0.61 to 1.18 that includes no effect. By histology, squamous tumours gave a hazard ratio of 0.65 and non-squamous tumours 0.79, the latter with a range of 0.55 to 1.14. Akeso adds that squamous disease made up 45.5 percent of the trial population and that, among squamous patients on ivonescimab, 72.2 percent had central tumours, 10.0 percent had cavitation or necrosis and 6.7 percent had tumours encasing major vessels, groups usually kept away from drugs that block VEGF over bleeding risk; the company says it saw no apparent increase in bleeding in them. That assessment remains the developer's own reading of its data.[1], [2]
More treatment-related side effects, similar discontinuation rates
Treatment-related adverse events of any grade affected 93.4 percent of patients on ivonescimab and 84.9 percent on pembrolizumab, and serious treatment-related events 29.9 percent against 21.6 percent. Events that forced permanent discontinuation were reported in 4.1 percent versus 5.0 percent, and immune-related adverse events in 34.0 percent versus 33.7 percent, so the safety profiles stayed broadly comparable with longer follow-up. The overall survival readout is the trial's key secondary endpoint; HARMONi-2 had already met its primary endpoint of progression-free survival, 11.1 months against 5.8 months with a hazard ratio of 0.51, and that result underpinned ivonescimab's approval in China for this indication in April 2025. The trial ran only in China, and what exists so far is a conference abstract; there is no journal publication yet. Akeso says the abstract data appeared on the WCLC website on 13 September, that the principal investigator Caicun Zhou of Shanghai East Hospital gives the formal oral presentation on 15 September, and that a multinational phase 3 trial, HARMONi-7, is testing ivonescimab against pembrolizumab in PD-L1-high disease.[1], [2]
