As reported in The Lancet by Lu et al, an interim analysis of the Chinese phase III HARMONi-6 trial showed that ivonescimab plus chemotherapy was associated with significantly improved overall survival vs tislelizumab plus chemotherapy in patients with previously untreated advanced squamous non–small cell lung cancer (NSCLC). A prior report from the trial showed that progression-free survival, the primary endpoint, was significantly better with ivonescimab plus chemotherapy.
Study Details
In the multicenter double-blind trial, 532 patients 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), both with carboplatin AUC = 5 and paclitaxel at 175 mg/m2 every 3 weeks for four cycles, followed by maintenance ivonescimab or tislelizumab at the same doses every 3 weeks. Treatment was continued for up to 24 months or until absence of clinical benefit, unacceptable toxicity, or initiation of new antitumor treatment. Patients had a median age of 64 years (interquartile range = 59–69 years). Overall survival was a key secondary endpoint.
Key Findings
At data cutoff (end of February 2026), death had occurred in 84 patients (32%) in the ivonescimab group vs 120 patients (45%) in the tislelizumab group. At a median follow-up of 21.4 months (95% confidence interval [CI] = 20.27–21.91 months), median overall survival was 27.9 months (95% CI = 27.89 months to not evaluable) in the ivonescimab group vs 23.7 months (95% CI = 20.11 months to not evaluable) in the tislelizumab group (hazard ratio = 0.66, 95% CI = 0.50–0.87, P =.0017), meeting the prespecified significance boundary (P < .0049).
Grade 3 or higher treatment-related adverse events occurred in 69% of the ivonescimab group vs 59% of the tislelizumab group, most commonly decreased neutrophil count (32% vs 26%), decreased white blood cell count (11% vs 9%), and anemia (7% vs 5%). Grade 3 or higher hemorrhage occurred in seven patients (3%) vs two patients (1%). Treatment-related adverse events led to discontinuation of ivonescimab in 5% of patients and discontinuation of tislelizumab in 5%. Treatment-related adverse events leading to death occurred in 10 patients (4%) vs 11 patients (4%).
The investigators concluded: “Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival compared with tislelizumab plus chemotherapy in previously untreated patients with advanced squamous NSCLC. This regimen could provide a novel treatment option as first-line treatment in this patient group.”
Shun Lu, MD, of Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China, is the corresponding author for The Lancet article.
DISCLOSURE: The study was funded by Akeso Biopharma. For full disclosures of the study authors, visit thelancet.com.
