Ivonescimab Plus Chemotherapy as a Potential New Standard of Care for Advanced Squamous Non-Small Cell Lung Cancer
According to results from the phase 3 HARMONi-6 trial, ivonescimab plus chemotherapy significantly improved survival compared to tislelizumab plus chemotherapy among patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC).
These data were presented by Shun Lu, MD, PhD, Shanghai Chest Hospital, China, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In previous reports, ivonescimab yielded significantly improved progression-free survival (PFS) over pembrolizumab as first-line therapy for advanced NSCLC in patients with a PD-L1 tumor proportion score ≥1%. The phase 3 HARMONi-6 trial aimed to compare ivonescimab plus chemotherapy vs tislelizumab plus chemotherapy in squamous NSCLC regardless of PD-L1 expression.
The study enrolled 532 previously untreated patients with stage IIIB to IV squamous NSCLC. Patients were randomized 1:1 to receive either 20 mg/kg of ivonescimab (n = 266) or 200 mg of tislelizumab (n = 266) once every 3 weeks plus 4 cycles of paclitaxel (175 mg/m²) and carboplatin (AUC 5) followed by maintenance ivonescimab or tislelizumab. Patients were stratified based on disease stage and PD-L1 tumor proportion score.
The primary trial end point was progression-free survival (PFS) and a key secondary end point was safety.
At analysis, median PFS was 11.1 months in the ivonescimab arm and 6.9 months in the tislelizumab arm (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46 to 0.78; P <.0001). In patients with a PD-L1 tumor proportion score of <1%, median PFS was 9.9 months in the ivonescimab arm and 5.7 months in the tislelizumab arm. In patients with a PD-L1 tumor proportion score of ≥1%, median PFS was 12.6 months in the ivonescimab arm and 8.6 months in the tislelizumab arm.
Treatment-related adverse events occurred in 32.3% of patients in the ivonescimab arm and 30.2% of patients in the tisleizumab arm . Grade ≥3 hemorrhagic events occurred in 1.9% and 0.8% of patients, respectively.
Dr Lu et al noted that these results suggest the potential of ivonescimab and chemotherapy as a new first-line standard of care for advanced/metastatic squamous NSCLC.
Source:
Lu S, Yang F, Jiang Z, et al. Phase III Study of Ivonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as First-line Treatment for advanced squamous non-small cell lung cancer (HARMONi-6). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA4
