Multicenter phase 3 trial of ivonescumab versus pembrolizumab for PD-L1-positive advanced non-small cell lung cancer

Ivonescimab is a bispecific antibody against PD-1 and VEGFR. The phase 3 HARMONi-2 trial, at 55 centers in China, compared ivonescimab with pembrolizumab for previously untreated PD-L1 positive advanced non-small cell lung cancer. At the preplanned interim analysis, the median progression-free survival was signicantly longer with ivonescimab than with pembrolizumab (11.1 versus 5.8 months; HR 0.51; 95% CI 0.38-0,69). The PFS benefit with ivonescimab over pembrolizumab was consistent within prespecified subgroups, including patients with PD-L1 TPS 1-49% (HR 0.54; 95% CI 0.37-0.78) and patients with PD-L1 TPS of 50% or higher (0.48; 0.29-0.79). Grade 3 or higher treatment-related adverse events occurred in 29% of patients receiving ivonescimab and 16% of patients receiving pembrolizumab. Ivonescimab demonstrated a manageable safety profile in patients with squamous NSCLC as well as patients with nonsquamous NSCLC. The authors conclude that ivonescimab significantly improved PFS compared with pembrolizumab in previously untreated patients with advanced PD-L1 positive NSCLC.