In an interim analysis of a Chinese phase III trial (HARMONi) reported in The Lancet, Xiong et al found that ivonescimab—a bispecific antibody against PD-1 and VEGF—significantly improved progression-free survival vs pembrolizumab in the first-line setting for patients with advanced PD-L1–positive non–small cell lung cancer (NSCLC).
Study Details
In the multicenter, double-blind trial, 398 patients were randomly assigned between November 2022 and August 2023 to receive ivonescimab at 20 mg/kg (n = 198) or pembrolizumab at 200 mg (n = 200) every 3 weeks. The primary endpoint of the study was progression-free survival on masked independent radiographic review.
Key Findings
At preplanned interim analysis, median progression-free survival was 11.1 months (95% confidence interval [CI] = 7.3 months to not estimable) with ivonescimab vs 5.8 months (95% CI = 5.0–8.2 months) with pembrolizumab (stratified hazard ratio [HR] = 0.51, 95% CI = 0.38–0.69, P < .0001). The progression-free survival benefit of ivonescimab was consistent among subgroups, including patients with a PD-L1 tumor proportion score (TPS) of 1% to 49% (HR = 0.54, 95% CI = 0.37–0.78) and those with a PD-L1 TPS of ≥ 50% (HR = 0.48, 95% CI = 0.29–0.79).
Grade ≥ 3 treatment-related adverse events occurred in 29% of those in the ivonescimab group, most commonly hypertension (5%), and 16% of the pembrolizumab group, most commonly hyperglycemia (1%). Serious treatment-related adverse events were reported in 21% vs 16% of patients. Immune-related grade ≥ 3 adverse events occurred in 7% vs 8% of patients.
The investigators stated: “Ivonescimab demonstrated a manageable safety profile in patients with both squamous and nonsquamous NSCLC. In patients with squamous cell carcinoma, grade 3 or higher treatment-related adverse events were comparable between the two groups.”
They concluded: “Ivonescimab significantly improved [progression-free survival] compared with pembrolizumab in previously untreated patients with advanced PD-L1–positive NSCLC. Therefore, ivonescimab might represent another treatment option in the first-line setting for [this lung cancer subtype].”
Caicun Zhou, MD, of Shanghai Pulmonary Hospital, Tongji University, Shanghai, is the corresponding author of The Lancet article.
Disclosure: The study was funded by Akeso Biopharma. For full disclosures of the study authors, visit thelancet.com.
