Akeso’s bispecific antibody ivonescimab significantly improved overall survival in the Phase 3 HARMONi‑6 trial for advanced squamous NSCLC, reducing risk of death by 34% versus tislelizumab plus chemotherapy. Results were presented at ASCO 2026 and published in The Lancet.
Written By: Disha Jadhav, BPharm
Fact Checked By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Akeso reported positive Phase 3 HARMONi-6 (NCT05840016) results showing that ivonescimab plus chemotherapy significantly improved overall survival compared with tislelizumab plus chemotherapy in patients with advanced squamous non-small cell lung cancer (sq-NSCLC). Findings were highlighted during a Plenary Session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The Lancet, underscoring the importance of the results within the global oncology community.
Dual PD-1/VEGF Targeting
Ivonescimab is a bispecific antibody that targets programmed death-1 (PD-1) and vascular endothelial growth factor (VEGF). The therapy combines immune checkpoint inhibition with anti-angiogenic activity to enhance antitumor immune responses while limiting tumor blood vessel formation. This approach addresses persistent unmet needs in advanced squamous NSCLC, where long-term survival outcomes remain suboptimal despite widespread use of PD-1 inhibitor-based regimens.
Trial Design and Patient Population
The HARMONi-6 study enrolled 532 patients with advanced sq-NSCLC. Progression-free survival (PFS) served as the primary endpoint and was previously met, with ivonescimab plus chemotherapy demonstrating a median PFS of 11.1 months compared with 6.9 months for tislelizumab plus chemotherapy (HR=0.60; P<0.0001). Overall survival (OS) was a key secondary endpoint and has now been confirmed at the prespecified interim analysis.
Efficacy Results
Median overall survival reached 27.9 months with ivonescimab plus chemotherapy compared with 23.7 months for tislelizumab plus chemotherapy. The regimen reduced the risk of death by 34% (HR=0.66; 95% CI, 0.50–0.87; P=0.0017). The 24-month overall survival rate was 64.7% in the ivonescimab arm versus 48.6% in the control arm.
The survival benefit remained consistent across predefined patient subgroups, including those with low PD-L1 expression and patients with a higher metastatic burden.
Safety Profile
Grade ≥3 treatment-related adverse events occurred in 69.2% of patients receiving ivonescimab and 58.9% of those receiving tislelizumab. Rates of treatment discontinuation and treatment-related deaths were similar between treatment groups, supporting the overall safety profile observed in the study.
Clinical Impact
Shun Lu, MD, Director of the Lung Cancer Center at Shanghai Chest Hospital and principal investigator of the study, highlighted that HARMONi-6 is among the first Phase 3 trials in advanced squamous NSCLC to demonstrate statistically significant improvements in both progression-free survival and overall survival compared with a PD-1-based chemotherapy regimen.
Akeso Founder, Chairwoman, President and CEO Yu Xia, MD, said the study marks the first successful Phase 3 head-to-head demonstration of both overall survival and progression-free survival superiority over a PD-1 plus chemotherapy regimen. She noted that the results further strengthen confidence in ivonescimab’s potential across multiple lung cancer settings and support ongoing global development efforts.
The findings position ivonescimab among a small group of investigational therapies that have demonstrated meaningful improvements in both major survival endpoints in this treatment setting.
Regulatory and Development Outlook
Ivonescimab is currently being evaluated in more than 30 clinical programs, including 15 Phase 3 studies across multiple tumor types and lung cancer settings. Akeso and its partner Summit Therapeutics continue to advance global development of the PD-1/VEGF bispecific antibody while evaluating potential regulatory pathways across major markets, including the United States, Europe, and China.
The HARMONi-6 results add to a growing body of evidence supporting ivonescimab across multiple lung cancer settings and further strengthen its potential role in frontline treatment of advanced squamous NSCLC.
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About the Writer
Disha Sanjay Jadhav (LinkedIn) is a pharmacy graduate and healthcare writer with a strong interest in clinical documentation and simplifying healthcare information for better reader understanding. She is enthusiastic, adaptable, and eager to take on new challenges while contributing to clear, accurate, and engaging medical and pharmaceutical content.