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

PURPOSE This study aimed to evaluate the safety and efficacy of ivonescimab (a bispecific antibody against programmed death-1 [PD-1] and vascular endothelial growth factor [VEGF]) as first- or second-line monotherapy in advanced immunotherapy naïve non-small-cell lung cancer (NSCLC) patients. METHODS Eligible patients received intravenous ivonescimab 10mg/kg every 3 weeks (Q3W), 20 mg/kg every 2 weeks (Q2W), 20 mg/kg Q3W or 30mg/kg Q3W. The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1. RESULTS At data cutoff (October 5, 2022), 108 patients were enrolled and received ivonescimab. Programmed death ligand-1 (PD-L1) tumor proportion score (TPS) was ≥1% in 74 (68.5%) patients, including 35 (32.4%) with TPS ≥50%. The median follow-up was 10.4 months (range 8.4 to 10.9 months). For all patients, ORR and disease control rate (DCR) were 39.8% and 86.1%, respectively. ORR by TPS was 14.7%, 51.4% and 57.1% in patients with TPS <1%, ≥1%, and ≥50%, respectively. In the 67 PD-L1 positive patients receiving first-line ivonescimab, the ORR was 33.3%, 52.6%, 60.0%, and 75.0% at the doses of 10mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W and 30mg/kg Q3W, respectively. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 24 (22.2%) patients. TRAEs leading to treatment discontinuation occurred in 1 (0.9%) patient. TRAEs leading to death occurred in 3 (2.8%) patients with squamous histology. The occurrence of grade ≥3 TRAEs and grade ≥3 bleeding events in squamous versus non-squamous histologies were 25.5% vs. 18.9% and 0.0% vs. 1.9%, respectively. CONCLUSION Ivonescimab monotherapy was well tolerated and demonstrated promising efficacy in patients with advanced or metastatic NSCLC.