On March 7, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that the groundbreaking results of the Phase III clinical study (HARMONi-2/AK112-303) of its first-in-class PD-1/VEGF bispecific antibody, ivonescimab, as a monotherapy compared to pembrolizumab monotherapy in the first-line treatment of PD-L1 positive (PD-L1 TPS ≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC) have been published in The Lancet (Press release, Akeso Biopharma, MAR 7, 2025, View Source [SID1234651020]).

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The Lancet is a prestigious international medical journal, and the publication of the HARMONi-2 study results in The Lancet is a strong recognition by the academic community to the breakthrough clinical potential of ivonescimab. Previously, clinical research on using ivonescimab for the treatment of various malignant tumors has been published in renowned international medical journals such as JAMA, Journal of Thoracic Oncology, eClinical Medicine (a sub-journal of The Lancet), and Drugs.

At the 2024 World Conference on Lung Cancer (WCLC), the results of the HARMONi-2 study were presented as an oral report by the principal investigator of the study, Professor Zhou Caicun, a renowned oncology expert who is the President-Elect of IASLC, and the director of the Department of Oncology at the Shanghai East Hospital, Tongji University.

The HARMONi-2 study demonstrated that in the intent-to-treat population, ivonescimab monotherapy significantly extended progression-free survival (PFS) compared to pembrolizumab monotherapy, reducing the risk of disease progression by 49% (PFS HR 0.51, P<0.0001). Subgroup analyses revealed that regardless of patients’ age, gender, ECOG performance status, PD-L1 expression, histological type, or the presence of liver or brain metastases, the ivonescimab group showed significant improvement in efficacy compared to the pembrolizumab group. The ivonescimab HARMONi-2 study is the world’s first randomized, double-blind, controlled Phase III clinical trial to achieve significantly positive results compared to pembrolizumab.

Based on these promising results, the sNDA for ivonescimab monotherapy as a first-line treatment for PD-L1 positive NSCLC is under review with priority status in China. Ivonescimab in combination with chemotherapy for EGFR-TKI-resistant non-squamous NSCLC, has already been approved and included in the 2024 China National Reimbursement Drug List. The growing body of clinical evidence from multiple Phase II and Phase III studies continues to validate ivonescimab’s efficacy benefit and safety profile. These results are often published in major international conferences and in top-tier journals, providing oncologists strong scientific basis for treatment decisions.

Akeso has strategically positioned ivonescimab within a comprehensive development plan, aiming to reshape the landscape of cancer immunotherapy and establish a new global standard of care. Ivonescimab, in combination with chemotherapy, has been approved in China for the treatment of EGFR-TKI-resistant, non-squamous NSCLC. The New Drug Application (sNDA) for ivonescimab monotherapy as a first-line treatment for PD-L1-positive NSCLC (in comparison to pembrolizumab) is currently under review and has been granted priority status in China.

Three international multicenter Phase III clinical trials, led by our partner Summit Therapeutics, are progressing efficiently or are being initiated:

The HARMONi study, an international multicenter Phase III clinical trial evaluating ivonescimab in combination with chemotherapy for non-squamous NSCLC with progression after third-generation EGFR-TKI treatment, has had patient enrollment completed and has received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA),
The HARMONi-3 study, an international multicenter Phase III clinical trial comparing ivonescimab combined with chemotherapy as first-line treatment for both squamous and non-squamous NSCLC (versus pembrolizumab combined with chemotherapy),
The HARMONi-7 study, an international multicenter Phase III clinical trial evaluating ivonescimab monotherapy as first-line treatment for PD-L1 high-expressing NSCLC (versus pembrolizumab).
Several Phase III clinical trials are progressing efficiently or are being initiated in China, including:

Ivonescimab combined with chemotherapy as first-line treatment for squamous NSCLC (vs. tislelizumab combined with chemotherapy, HARMONi-6/AK112-306),
Ivonescimab combined with chemotherapy as first-line treatment for biliary tract cancer (vs. durvalumab combined with chemotherapy, HARMONi-GI1/AK112-309),
Ivonescimab combined with AK117 (CD47) as first-line treatment for PD-L1 positive head and neck squamous cell carcinoma (vs. pembrolizumab, SOLO-10/AK117-302),
First-line treatment for triple-negative breast cancer (HARMONi-BC1/AK112-308).