In an interim analysis of a Chinese phase III trial (HARMONi-6) reported in The Lancet, Chen et al found that the combination of ivonescimab—a bispecific antibody targeting PD-1 and VEGF—plus chemotherapy prolonged progression-free survival vs tislelizumab—an anti–PD-1 monoclonal antibody—plus chemotherapy in first-line treatment of advanced squamous non–small cell lung cancer (NSCLC).
Study Details
In the multicenter double-blind trial, 761 patients with unresectable stage IIIB or IIIC or stage IV disease were randomly assigned between August 2023 and January 2025 to receive ivonescimab at 20 mg/kg (n = 266) or tislelizumab at 200 mg (n = 266) with paclitaxel at 175 mg/m2 and carboplatin AUC = 5 once every 3 weeks for four cycles followed by ivonescimab at 20 mg/kg or single-agent tislelizumab at 200 mg as maintenance treatment for up to 24 months. A total of 105 patients (39%) in the ivonescimab group and 105 (39%) in the tislelizumab group had a PD-L1 tumor proportion score (TPS) < 1%. The primary endpoint was progression-free survival on independent radiographic review committee assessment.
Key Findings
Median progression-free survival was 11.1 months (95% confidence interval [CI] = 9.9 months to not evaluable) in the ivonescimab group vs 6.9 months (95% CI = 5.8–8.6 months) in the tislelizumab group (hazard ratio [HR] = 0.60, 95% CI = 0.46–0.78, P < .0001). Rates at 9 and 12 months were 62% vs 43% and 48% vs 35%.
Median progression-free survival was 9.9 vs 5.7 months in patients with PD-L1 TPS < 1% (HR = 0.55, 95% CI = 0.37–0.82), 12.6 vs 8.6 months among those with PD-L1 TPS ≥ 1% (HR = 0.66, 95% CI = 0.46–0.95), 12.6 vs 6.9 months among those with PD-L1 TPS of 1%–49% (HR = 0.63, 95% CI = 0.41–0.98), and 12.6 vs 9.7 months among those with PD-L1 TPS ≥ 50% (HR = 0.71, 95% CI = 0.37–1.33).
Grade ≥ 3 treatment-related adverse events occurred in 64% of the ivonescimab group vs 54% of the tislelizumab group; the most common were decreased neutrophil count (32% vs 26%), decreased white blood cell count (11% vs 9%), and anemia (6% vs 4%). Grade ≥ 3 treatment-related hemorrhage occurred in five patients (2%) vs two patients (1%). Grade ≥ 3 immune-related adverse events occurred in 9% vs 10% of patients. Treatment-related adverse events led to discontinuation of ivonescimab in 3% of patients and tislelizumab in 4% of patients. Treatment-related adverse events led to death in eight (3%) and ten patients (4%).
The investigators concluded: “In patients with untreated advanced squamous NSCLC, ivonescimab plus chemotherapy showed significantly improved progression-free survival compared with tislelizumab plus chemotherapy, regardless of PD-L1 status, as well as a manageable safety profile. This regimen could be used as a novel first-line treatment in this patient group.”
Shun Lu, MD, of Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Akeso Biopharma. For full disclosures of all study authors, visit thelancet.com.
