The survival finding builds on HARMONi-2’s earlier progression-free survival results, which had already demonstrated a statistically significant benefit for ivonescimab over pembrolizumab. In that prior analysis, 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). Those data supported regulatory approval of ivonescimab in China for this patient population in April 2025. Overall survival served as the trial’s key secondary endpoint, and the new late-breaking analysis provides mature survival data to complement the earlier efficacy signal.

The randomized trial enrolled 398 patients at centers in China between November 2022 and August 2023. Eligible participants had treatment-naive, locally advanced or metastatic NSCLC with a PD-L1 tumor proportion score of at least 1% and no EGFR or ALK alterations. Patients were randomized 1:1 to receive ivonescimab 20 mg/kg (n=198) or pembrolizumab 200 mg (n=200) every three weeks, placing the two regimens in a direct head-to-head comparison.

The overall survival benefit was generally consistent across prespecified subgroups, though with some variation in magnitude. Among patients with squamous histology, the hazard ratio was 0.65 (95% CI, 0.45-0.95), while those with non-squamous histology showed a hazard ratio of 0.79 (95% CI, 0.55-1.14). In the subgroup analysis by PD-L1 expression level, patients with a tumor proportion score of 1-49% had a hazard ratio of 0.85 (95% CI, 0.61-1.18), whereas patients with a score of at least 50% showed a hazard ratio of 0.58 (95% CI, 0.38-0.89), a pattern indicating a more pronounced point estimate in tumors with higher PD-L1 expression, though the confidence interval in the lower-expression subgroup crossed 1.

Safety profiles were broadly comparable between the treatment groups over extended follow-up. Any-grade treatment-related adverse events occurred in 93.4% of patients receiving ivonescimab and 84.9% of those receiving pembrolizumab. Serious treatment-related adverse events were reported in 29.9% and 21.6% of patients, respectively. Treatment-related adverse events leading to permanent discontinuation occurred in 4.1% of the ivonescimab group versus 5.0% of the pembrolizumab group, and immune-related adverse events were nearly identical at 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 of 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.”

Ivonescimab is a bispecific antibody designed to target both the PD-1 checkpoint pathway and VEGF, the molecular basis cited in the trial’s design for comparing it against pembrolizumab monotherapy. The head-to-head phase 3 comparison demonstrated a statistically significant overall survival advantage in a population defined by PD-L1 expression of at least 1% and the absence of EGFR or ALK alterations, with the median survival difference amounting to more than eight months.

The subgroup patterns, including the wider confidence intervals in the non-squamous and PD-L1 1-49% strata, delineate where the survival benefit was estimated with greater or lesser precision in this trial. The data were presented as a late-breaking analysis at the conference, which gathers nearly 7,000 researchers, physicians, and specialists from more than 100 countries and is dedicated to lung cancer and other thoracic malignancies.

As an interim analysis with 234 overall survival events at the prespecified cutoff, the findings reflect the maturity of the survival data available at that point in the trial. Within the studied population in China, the results consolidate the evidence base for ivonescimab, which secured its Chinese approval on the strength of the earlier progression-free survival data and now carries overall survival results from the same randomized comparison.

Subject of Research: Phase 3 HARMONi-2 trial of ivonescimab versus pembrolizumab as first-line treatment for PD-L1-positive advanced non-small cell lung cancer

Article Title: Late-breaking HARMONi-2 analysis shows ivonescimab significantly improves overall survival versus pembrolizumab in PD-L1-Positive Advanced NSCLC

Article References: Late-breaking HARMONi-2 analysis shows ivonescimab significantly improves overall survival versus pembrolizumab in PD-L1-Positive Advanced NSCLC. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: ivonescimab, pembrolizumab, HARMONi-2, non-small cell lung cancer, PD-L1, overall survival, immunotherapy, bispecific antibody, phase 3 trial, IASLC, WCLC 2026, Late-breaking