Ivonescimab versus pembrolizumab in PD-L1-positive non-small cell lung cancer

The new bispecific antibody ivonescimab improved clinical results compared with pembrolizumab in previously untreated patients with programmed cell death ligand-1 (PD-L1)-positive advanced non-small cell lung cancer, as recently shown on The Lancet.

Ivonescimab is a bispecific antibody against PD-L1 and vascular endothelial growht factor with promising clinical outcomes in early phase studies. The HARMONi-2 trial, a randomised, double-blind, phase 3 study, compared ivonescimab (20 mg/kg) with pembrolizumab (200 mg/kg) in 398 previously untreated patients with locally advanced or metastatic PD-L1-positive non-small cell lung cancer. Median progression-free survival was of 11.1 versus 5.8 months with ivonescimab and pembrolizumab, respectively, with a benefit broadly consistent within subgroups with different PD-L1 expression and also in patients with squamous and non-squamous non-small cell lung cancer. Grade 3 or higher treatment-related adverse events occurred in 29% of patients with ivonescimab and 16% of patients with pembrolizumab; immune-related adverse events of grade 3 or higher were similar between the ivonescimab and pembrolizumab groups and ivonescimab demonstrated a manageable safety profile. As authors conclude «Ivonescimab significantly improved progression-free survival with a manageable safety profile as first-line treatment in patients with locally advanced or metastatic PD-L1-positive non-small cell lung cancer, and could thus provide a novel treatment option for these patients, regardless of non-small cell lung cancer histology. We are actively expanding the array of clinical trials testing ivonescimab alone and in various combinations, both in non-smallcell lung cancer and in other tumor types in a global setting».