(SEOUL, Republic of Korea — Sept. 13th at 10:45 a.m. Korea Standard Time) — 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.” said Prof. Caicun Zhou, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. “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.”
About the IASLC
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in more than 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC
The WCLC is the world's largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration, and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit wclc.iaslc.org.
###