Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial.

BackgroundSquamous non-small-cell lung cancer (NSCLC) is associated with worse clinical outcomes than non-squamous NSCLC, but treatment options are scarce. We aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC.MethodsWe conducted a randomised, double-blind, phase 3 trial at 50 sites across China (HARMONi-6). Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive intravenous ivonescimab (20 mg/kg) or tislelizumab (200 mg), plus intravenous paclitaxel (175 mg/m2) and carboplatin (area under the curve 5 mg/mL per min) once every 3 weeks for four cycles, followed by ivonescimab (20 mg/kg) or tislelizumab (200 mg) monotherapy as maintenance treatment for up to 24 months. Randomisation was stratified by disease stage (IIIB or IIIC vs IV) and PD-L1 tumour proportion score (≥1% vs