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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, December 1, 2025
The bispecific monoclonal antibody ivonescimab has been shown to significantly improve progression-free survival compared with pembrolizumab as first-line therapy for advanced non–small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score of at least 1%. Interim results of the phase III HARMONi-6 trial, presented during the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract LBA4) by Shun Lu, MD, PhD, of Shanghai Jiao Tong University, and colleagues, demonstrated this benefit when the agent vs tislelizumab-jsgr was combined with chemotherapy in patients with squamous NSCLC and any PD-L1 expression level.
A total of 532 patients with untreated stage IIIB to IV squamous NSCLC were randomly assigned in a 1:1 ratio to receive four cycles of paclitaxel and carboplatin plus either ivonescimab or tislelizumab once every 3 weeks. This regimen was followed by maintenance monotherapy with either ivonescimab or tislelizumab. Randomization was stratified by disease stage (IIIB/IIIC vs IV) and PD-L1 tumor proportion score (≥ 1% vs < 1%).
Ivonescimab vs tislelizumab demonstrated a statistically significant improvement in progression-free survival (hazard ratio [HR] = 0.60; P < .0001). The median durations were 11.1 vs 6.9 months, respectively, as assessed by independent radiographic review committee. The investigators observed consistent benefit across key subgroups. In patients with a PD-L1 tumor proportion score of less than 1%, the median progression-free survival was 9.9 months with ivonescimab and 5.7 months with tislelizumab (HR = 0.55); it was 12.6 and 8.6 months, respectively, in those with scores of at least 1% (HR = 0.66).
Based on safety analyses, treatment-related serious adverse events occurred in 32.3% of patients treated with ivonescimab and 30.2% of those who received tislelizumab. Hemorrhagic events of grade 3 or higher were reported in 1.9% and 0.8% of the arms, respectively.
“This phase III trial result suggests first-line ivonescimab [plus] chemotherapy may be a new standard of care for advanced or metastatic squamous NSCLC,” the investigators commented.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
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