Akeso Biopharma has announced the enrollment of the first patient in a Phase 3 clinical trial (AK117-302) assessing the efficacy and safety of ivonescimab in combination with ligufalimab for the first-line treatment of head and neck squamous cell carcinoma (HNSCC). The randomized, controlled, multicenter study compares the combination of Akeso's PD-1/VEGF bispecific antibody, ivonescimab, and its next-generation CD47 monoclonal antibody, ligufalimab (AK117), to pembrolizumab in patients with PD-L1 positive (CPS≥1) recurrent/metastatic HNSCC.
Significance of the AK117-302 Trial
The AK117-302 trial marks a significant milestone as the first Phase 3 clinical trial globally to investigate a CD47 monoclonal antibody therapy for solid tumors. This trial is the fifth Phase 3 study for ivonescimab utilizing PD-1/L1 monoclonal antibody therapy as a positive control, and the third Phase 3 study comparing ivonescimab with pembrolizumab. The trial underscores Akeso's commitment to advancing cancer immunotherapy and establishing a global standard of care for cancer treatment.
Unmet Needs in HNSCC Treatment
In 2022, there were 770,000 new cases of head and neck cancer globally, with 84,000 cases reported in China. Squamous cell carcinoma of the head and neck (HNSCC) accounts for over 90% of these cancers. The five-year survival rate for patients with recurrent/metastatic HNSCC (R/M HNSCC) is only 3.6%. While targeted therapies and immunotherapies have improved treatment options, the median overall survival (OS) remains below one year. Pembrolizumab is a first-line standard treatment for R/M HNSCC, but there remains a critical unmet need for more effective therapies to improve long-term survival.
Promising Early Data
At the 2024 European Society for Medical Oncology (ESMO) Congress, Akeso reported initial positive data on its combination therapy of ivonescimab and ligufalimab. This combination demonstrated significant tumor reduction and survival benefits, particularly for HNSCC patients, who require rapid tumor shrinkage. The preliminary efficacy data from this therapy surpassed that of previously disclosed PD-1 studies, positioning it as a potentially new immunotherapy option for HNSCC patients.
About Ligufalimab (AK117)
Ligufalimab (AK117) is a next-generation humanized IgG4 anti-CD47 antibody developed by Akeso without hemagglutination effect. AK117 binds to CD47 expressed on tumor cells, blocking the interaction between CD47 and SIRPα to enhance phagocytic activity of phagocytes on tumor cells, thereby inhibiting tumor growth. Several Phase 2 clinical trials are underway to investigate the potential of AK117 in combination with azacitidine for hematological tumors, as well as AK117 alone or in combination with ivonescimab and cadonilimab for various solid tumors. Preliminary studies have shown promising efficacy and safety profiles, with no observed dose-limiting toxicity events.
About Ivonescimab (AK112/SMT112)
Ivonescimab is a novel global first-in-class PD-1/VEGF bi-specific immunotherapy drug independently developed by Akeso. Ivonescimab was granted marketing approval by NMPA for the treatment of EGFR mutated locally advanced or metastatic non-squamous NSCLC patients who have progressed after EGFR TKI treatment. Akeso is conducting multiple clinical trials of ivonescimab covering 17 indications including gastrointestinal cancer, hepatocellular carcinoma and colorectal cancer.
