Ivonescimab significantly prolonged overall survival compared with pembrolizumab as first-line treatment for patients with PD-L1-positive advanced non-small cell lung cancer (NSCLC), according to a prespecified interim analysis of the phase 3 HARMONi-2 trial presented today at the IASLC 2026 World Conference on Lung Cancer.<\/p>\n
HARMONi-2 previously demonstrated a statistically significant progression-free survival benefit with ivonescimab, a first-in-class PD-1\/VEGF bispecific antibody, compared with pembrolizumab in treatment-naive patients with PD-L1-positive advanced NSCLC. Median progression-free survival was 11.1 months with ivonescimab versus 5.8 months with pembrolizumab (HR, 0.51; 95% CI, 0.38-0.69; P<0.0001). Based on these findings, ivonescimab received regulatory approval in China for this patient population in April 2025. The new analysis reports results for overall survival, the trial’s key secondary endpoint.<\/p>\n
The randomized trial enrolled 398 patients at centers in China between November 2022 and August 2023. Eligible patients had treatment-naive, locally advanced or metastatic NSCLC with PD-L1 tumor proportion score (TPS) of at least 1% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations. Patients were randomized 1:1 to receive ivonescimab 20 mg\/kg (n=198) or pembrolizumab 200 mg (n=200) every three weeks.<\/p>\n
At the August 20, 2026, data cutoff, 234 overall survival events had occurred. Median overall survival was 30.8 months with ivonescimab compared with 22.6 months with pembrolizumab (HR, 0.73; 95% CI, 0.57-0.95; P=0.009), representing a statistically significant survival benefit.<\/p>\n
The overall survival benefit was generally consistent across prespecified subgroups. The hazard ratio was 0.65 (95% CI, 0.45-0.95) among patients with squamous histology and 0.79 (95% CI, 0.55-1.14) among those with non-squamous histology. Among patients with PD-L1 TPS of 1-49%, the hazard ratio was 0.85 (95% CI, 0.61-1.18), while patients with PD-L1 TPS of at least 50% had a hazard ratio of 0.58 (95% CI, 0.38-0.89).<\/p>\n
Safety profiles were broadly comparable between the treatment groups. Any-grade treatment-related adverse events occurred in 93.4% of patients receiving ivonescimab and 84.9% receiving pembrolizumab. Serious treatment-related adverse events occurred in 29.9% and 21.6% of patients, respectively. Treatment-related adverse events leading to permanent discontinuation were reported in 4.1% versus 5.0%, and immune-related adverse events occurred in 34.0% versus 33.7%.<\/p>\n
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Ivonescimab significantly prolonged overall survival versus pembrolizumab in this patient population, and retained a comparable safety profile with extended follow-up. These findings further strengthen ivonescimab as a chemotherapy-free first-line option. Already approved in China, the favorable overall survival results consolidate its status as a standard of care therapy in this setting.”<\/p>\n
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Prof. Caicun Zhou, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China<\/p>\n
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