In a phase III study conducted in China, the bispecific antibody ivonescimab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with the PD-1 inhibitor pembrolizumab as a first-line treatment of PD-L1–positive advanced non–small cell lung cancer (NSCLC), according to Zhou et al. These findings from the HARMONi-2 study were presented by Caicun Zhou, MD, PhD, of Shanghai Pulmonary Hospital, at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer.1
About HARMONi-2
Ivonescimab is a bispecific antibody targeting both PD-1 and the vascular endothelial growth factor (VEGF). It showed activity as front-line therapy in the phase II AK112-202 study.2
The phase III HARMONi-2 trial randomly assigned 398 patients from 55 centers in China to receive either ivonescimab (20 mg/kg) or pembrolizumab (200 mg) every 3 weeks. Patients had untreated locally advanced or metastatic NSCLC, and their tumors were PD-L1–positive (tumor proportion score [TPS] ≥ 1%) but negative for EGFR mutations or ALK rearrangements.
Patient Subgroups
At the planned interim analysis, with a median follow-up of 8.7 months, patients treated with ivonescimab achieved a median progression-free survival of 11.14 months compared with 5.8 months observed with pembrolizumab, representing a 49% reduction in the risk of disease progression or death (hazard ratio [HR] = 0.51; P < .0001). At 9 months, the progression-free survival rate was 56% with ivonescimab vs 40% with pembrolizumab.
The drug’s benefit was consistent across various patient subgroups, as demonstrated by robust hazard ratios: PD-L1–low (TPS = 1%–49%), HR = 0.54; PD-L1–high (TPS ≥ 50%), HR = 0.46; nonsquamous histology, HR = 0.54; squamous histology, HR = 0.48. Objective response rates were 50.0% with ivonescimab and 38.5% with pembrolizumab. Disease control rates were 89.9% and 70.5%, respectively, according to study data.
Safety Profiles
Safety profiles for both treatments were comparable, with no new safety signals identified for ivonescimab. Treatment-related serious adverse events were reported in 20.8% of patients receiving ivonescimab and 16.1% of those receiving pembrolizumab. Grade ≥ 3 immune-related adverse events were also similar between the two groups. In patients with squamous cell carcinoma, grade ≥ 3 toxicities were comparable between the two groups, approximately 20%. Ivonescimab produced slightly more proteinuria, hypertension, and laboratory abnormalities. All VEGF-related adverse events were grades 1 to 3 in both arms. Ivonescimab was associated with a numerically longer time to deterioration of global status, whose median was not reached with ivonescimab and was about 10 months with pembrolizumab.
Investigators indicated that the findings from HARMONi-2 support the use of ivonescimab as a first-line treatment option for patients with PD-L1–positive advanced NSCLC.
DISCLOSURE: For full disclosure of study authors, visit IASLC.org.
REFERENCES
1. Zhou C, Chen J, Wu L, et al: Phase 3 study of ivonescimab (AK112) vs pembrolizumab as first-line treatment for PD-L1–positive advanced NSCLC: Primary analysis of HARMONi-2. 2024 World Conference on Lung Cancer. Abstract PL02.04. Presented September 8, 2024.
2. Wang L, Luo Y, Ren S, et al: 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. J Thorac Oncol 19:465-475, 2024.
