A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC.

Introduction: This study (HARMONi-5) aimed to evaluate the safety and efficacy of ivonescimab (a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor) as first- or second-line monotherapy in patients with advanced immunotherapy-naive NSCLC.

Methods: Eligible patients received intravenous ivonescimab 10 mg/kg every 3 weeks (Q3W), 20 mg/kg every 2 weeks (Q2W), 20 mg/kg Q3W, or 30 mg/kg Q3W. The primary end points were safety and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1.

Results: At data cutoff (October 5, 2022), 108 patients were enrolled and received ivonescimab. Programmed death ligand-1 tumor proportion score (TPS) was greater than or equal to 1% in 74 patients (68.5%), including 35 (32.4%) with TPS greater than or equal to 50%. The median follow-up was 10.4 months (range: 8.4-10.9 mo). For all patients, ORR and disease control rate were 39.8% and 86.1%, respectively. ORR by TPS was 14.7%, 51.4%, and 57.1% in patients with TPS less than 1%, greater than or equal to 1%, and greater than or equal to 50%, respectively. In the 67 programmed death ligand-1-positive patients receiving first-line ivonescimab, the ORR was 33.3%, 52.6%, 60.0%, and 75.0% at the doses of 10 mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W, and 30 mg/kg Q3W, respectively. Grade greater than or equal to 3 treatment-related adverse events (TRAEs) were observed in 24 patients (22.2%). TRAEs leading to treatment discontinuation occurred in one patient (0.9%). TRAEs leading to death occurred in three patients (2.8%) with squamous NSCLC. The occurrence of grade greater than or equal to 3 TRAEs and grade greater than or equal to 3 bleeding events in squamous versus nonsquamous NSCLC patients was 25.5% versus 18.9% and 0.0% versus 1.9%, respectively.

Conclusions: Ivonescimab monotherapy was well tolerated and found to have a promising efficacy in patients with advanced or metastatic NSCLC.

Clinicaltrials: gov identifier: NCT04900363.