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.
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.
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.
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.
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).
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%.
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."
Prof. Caicun Zhou, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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