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• Ivonescimab plus chemotherapy demonstrated a median PFS of 11.14 months, PFS HR=0.60, P < 0.0001.
• The absolute difference in median PFS between the two groups was 4.24 months (ΔPFS = 4.24 months), indicating significantly prolonged progression-free survival with ivonescimab combination therapy.
• Significant benefits were consistently observed with ivonescimab plus chemotherapy versus tislelizumab combination irrespective of PD-L1 expression.
• Ivonescimab combination therapy showed significant benefit over tislelizumab regimen in patients with or without liver metastases and with or without brain metastases.
• In the HARMONi-6 study, 92.3% of enrolled patients had stage IV disease, and approximately 63% had central-type squamous cell carcinoma.
• Ivonescimab demonstrated a favorable overall safety profile with no new safety signals identified.
• Overall survival (OS) data were not yet mature at the time of this analysis.
HONG KONG, Oct. 19, 2025 /PRNewswire/ -- Akeso (9926.HK) announced the groundbreaking results of the registrational Phase III clinical study (AK112-306/HARMONi-6) evaluating ivonescimab (PD-1/VEGF bispecific antibody), a globally first-in-class bispecific antibody developed by Akeso, in combination with chemotherapy versus tislelizumab combined with chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC). The study results were presented by Professor Lu Shun, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital and Professor of Medicine at Shanghai Jiaotong University, at the 2025 ESMO Presidential Symposium, and the results of the HARMONi-6 clinical trial were simultaneously published in The Lancet.
The HARMONi-6 study met its primary endpoint of progression-free survival (PFS), demonstrating a decisive and strong positive outcome with both statistically significant and clinically meaningful benefits. Ivonescimab plus chemotherapy substantially prolonged sq-NSCLC patient's progression-free survival compared to tislelizumab plus chemotherapy:
• The progression-free survival (PFS) hazard ratio (HR) was 0.60 (p < 0.0001) for ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy. The median PFS was 11.14 months in the ivonescimab combination group versus 6.90 months in the tislelizumab combination group, representing an absolute improvement of ΔPFS = 4.24 months.
• Consistent clinical benefits were observed across all PD-L1 expression subgroups. In the PD-L1 negative (TPS <1%) population, the PFS HR was 0.55 for ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy. In the PD-L1 positive (TPS ≥1%) population, the PFS HR was 0.66 for ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy.
• Regardless of liver or brain metastasis, ivonescimab combined with chemotherapy showed significant benefit over the tislelizumab-based regimen. Among patients with liver metastases, the PFS HR was 0.53; among those without liver metastases, the PFS HR was 0.64. For patients with ≥3 baseline metastatic sites, the PFS HR was 0.46, and for those with <3 baseline metastatic sites, the PFS HR was 0.64.
The ivonescimab group demonstrated a favorable overall safety profile with no new safety signals identified. The incidence of treatment-related serious adverse reactions and grade 3 or higher bleeding events was comparable to the tislelizumab regimen group. The most common adverse reactions were chemotherapy-associated myelosuppression.
The HARMONi-6 study enrolled 532 subjects, with balanced baseline characteristics between the two groups. 92.3% of subjects had clinical stage IV disease. The squamous carcinoma characteristics of enrolled patients reflected real-world clinical presentations, with central-type squamous carcinoma accounting for approximately 63% of the total patients (66.9% in the ivonescimab group vs. 59.4% in the tislelizumab group), consistent with real-world patient distribution. PD-L1 expression levels also reflected those seen in real-world clinical settings.
Approved in 2024, ivonescimab has demonstrated groundbreaking clinical value across dozens of clinical studies and real-world treatments involving over 40,000 patients. In the field of tumor immunotherapy, whether compared with PD-1 monotherapy or PD-1 combination chemotherapy (the current standard of care for many cancers), as well as in the field of anti-angiogenesis therapy compared to VEGF-targeted regimens, ivonescimab has demonstrated robust and superior clinical efficacy, highlighting its exceptional capacity to drive iterative advances in cancer treatment.
The encouraging results from the HARMONi-6 study have led to the review of a supplemental New Drug Application (sNDA) in China for ivonescimab in combination with chemotherapy as a first-line treatment for advanced squamous NSCLC. Meanwhile, the global enrollment for the international, multicenter Phase III HARMONi-3 trial, assessing ivonescimab as a first-line treatment for both squamous (sq-NSCLC) and non-squamous (nsq-NSCLC) non-small cell lung cancer is ongoing.
