Ivonescimab, a novel bispecific antibody targeting PD-1 and VEGF, has demonstrated promising anti-tumor activity and a manageable safety profile in Phase II trials when used in combination therapies for metastatic colorectal cancer (CRC), advanced triple-negative breast cancer (TNBC), and recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). These findings were presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2024, supporting the further clinical development of ivonescimab in solid tumor settings beyond metastatic non-small cell lung cancer (NSCLC).
Colorectal Cancer Results
In a Phase II randomized study (AK112-206) evaluating first-line treatment for metastatic microsatellite-stable (MSS) CRC, ivonescimab plus FOLFOXIRI (chemotherapy) with or without ligufalimab (anti-CD47 monoclonal antibody) showed high response rates. As of February 29, 2024, the group receiving ivonescimab plus FOLFOXIRI (n=22) had an overall response rate of 81.8% (95% CI: 59.7, 94.8) and a disease control rate of 100% (95% CI: 84.6, 100), with a median follow-up of 9 months. The group receiving ivonescimab plus ligufalimab plus FOLFOXIRI (n=18) had an overall response rate of 88.2% (95% CI: 63.6, 98.5) and a disease control rate of 100% (95% CI: 80.5, 100), with a median follow-up of 9.6 months. Median progression-free survival (PFS) was not reached in either group. The safety profile was acceptable, with serious treatment-related adverse events (TRAEs) occurring in 22.7% and 11.1% of patients, respectively. The most common TRAEs included anemia, proteinuria, and decreases in white blood cell and neutrophil counts.
Triple-Negative Breast Cancer Results
In a Phase II study (AK117-203) assessing first-line treatment for locally advanced or metastatic TNBC, ivonescimab plus chemotherapy (paclitaxel or nab-paclitaxel) demonstrated significant efficacy. As of May 31, 2024, 30 patients received the combination therapy with a median follow-up of 10.2 months. The overall response rate was 72.4%, and the disease control rate was 100%. Median PFS was 9.3 months (95% CI: 6.24, NE). Subgroup analysis based on PD-L1 CPS expression showed consistent disease control rates of 100% across different PD-L1 CPS levels. The safety profile was manageable, with serious TRAEs reported in 30% of patients, and the most common TRAEs were decreases in white blood cell and neutrophil counts, and increases in ALT and AST. Notably, 60% of patients had previously received taxane-based chemotherapy in the neoadjuvant or adjuvant setting.
Head and Neck Squamous Cell Carcinoma Results
In a Phase II study (AK117-201) evaluating first-line treatment for PD-L1 positive recurrent/metastatic HNSCC, ivonescimab with or without ligufalimab showed clinical benefit. As of March 19, 2024, patients receiving ivonescimab (n=10) had an overall response rate of 30.0% and a disease control rate of 80.0%, with a median follow-up of 3.3 months. Patients receiving ivonescimab plus ligufalimab (n=20) had an overall response rate of 60.0% and a disease control rate of 90.0%, with a median follow-up of 4.1 months. Median PFS was 5.0 months and 7.1 months, respectively. The safety profile was acceptable, with no patients discontinuing treatment due to TRAEs. Common TRAEs included proteinuria and dermatitis acneiform.
About Ivonescimab
Ivonescimab (SMT112/AK112) is a bispecific antibody that combines PD-1 blockade with VEGF inhibition in a single molecule. Its tetravalent structure and cooperative binding to PD-1 and VEGF may enhance its accumulation and binding affinity in the tumor microenvironment, potentially improving efficacy and reducing off-target effects. Ivonescimab is currently in multiple Phase III clinical trials, including studies in NSCLC. Summit Therapeutics is developing ivonescimab in NSCLC, with Phase III trials HARMONi and HARMONi-3 ongoing and HARMONi-7 planned for early 2025. Ivonescimab was approved for marketing authorization in China in May 2024.
