HARMONi-6 advances squamous NSCLC care
HARMONi-6 data show ivonescimab plus chemotherapy significantly improves survival versus tislelizumab plus chemotherapy in advanced squamous non–small-cell lung cancer (NSCLC).
Shun Lu (Shanghai Jiao Tong University, China) presented the results of this randomized, multicenter, double-blind phase 3 trial at the European Society for Medical Oncology (ESMO) Congress 2025 and noted this “might be a new standard of care for squamous NSCLC.”
Ivonescimab is a bispecific antibody that targets PD-1 and vascular endothelial growth factor (VEGF). While it is already approved for non-squamous NSCLC in China, HARMONi-6 aimed to address unmet needs in squamous NSCLC.
Lu reported the median progression-free survival (PFS) was 11.14 months with ivonescimab plus chemotherapy (n=266), significantly longer than 6.90 months with tislelizumab plus chemotherapy (n=265; HR, 0.60). This PFS benefit was consistent across all key patient subgroups. In addition, Lu noted that the ivonescimab arm showed a meaningful improvement in PFS regardless of PD-L1 expression. Overall survival (OS) data remain immature.
Tumor response was significantly higher and more durable in the ivonescimab arm, with a duration of response of 11.20 months versus 8.38 months with tislelizumab.
Safety data in HARMONi-6 were consistent with previous HARMONi studies. Grade 3 treatment-related adverse events (TRAEs) occurred in 63.9% of participants in the ivonescimab arm and 54.3% in the tislelizumab arm. While similar immune-related AEs were observed for ivonescimab and tislelizumab, more VEGF-related AEs occurred with ivonescimab – the majority of which were grade 1–2.
Discussant Myung-Ju Ahn (Sungkyunkwan University School of Medicine, Seoul, South Korea) commented that this trial “sets a new benchmark in the management of squamous NSCLC.” However, she also raised the question “Can this PFS translate to OS? We still don’t know.”
Ahn noted that as this is a China-only study it will need global validation across diverse populations and concluded that “the real-world application will require multidisciplinary vigilance.”
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