Summit Therapeutics and Akeso Report Ivonescimab Survival Benefit

Miami, Florida, USA, September 2, 2026

HARMONi-2 Shows Overall Survival Improvement

The HARMONi-2 study, also designated AK112-303, evaluated ivonescimab as a single-agent treatment against pembrolizumab monotherapy in patients with locally advanced or metastatic NSCLC whose tumors expressed PD-L1. According to Summit, the preplanned OS analysis demonstrated a statistically significant improvement for ivonescimab compared with pembrolizumab. The result builds on the study’s earlier primary analysis, which demonstrated a statistically significant improvement in progression-free survival (PFS) by Independent Radiologic Review Committee assessment. In that analysis, ivonescimab achieved a hazard ratio of 0.51, with a 95% confidence interval of 0.38 to 0.69 and a p-value below 0.0001. The PFS benefit was reported across several clinical subgroups, including patients with low or high PD-L1 expression and both squamous and non-squamous disease.

Ivonescimab Combines PD-1 and VEGF Targeting

Ivonescimab, known as SMT112 in Summit’s licensed territories and AK112 outside those territories, is an investigational bispecific antibody engineered to combine PD-1 immune checkpoint blockade with VEGF inhibition in a single molecule. The drug is designed to interact cooperatively with both targets, with its binding characteristics intended to support greater engagement with PD-1 in the presence of VEGF. Summit states that the molecule’s engineered tetravalent structure, containing four binding sites, is intended to increase avidity within the tumor microenvironment where PD-1 and VEGF may be more highly expressed than in normal tissues. The approach is being developed as a potential way to combine immune-mediated antitumor activity with anti-angiogenic effects through one therapeutic molecule.

Broad Phase III Program Expands Oncology Development

The HARMONi-2 findings form part of a broader Phase III clinical development program for ivonescimab. Summit and Akeso are studying the therapy across multiple cancer settings, with 16 Phase III studies announced, ongoing, or completed according to the company. These programs include different NSCLC populations as well as colorectal cancer, urothelial carcinoma, biliary tract cancer, head and neck squamous cell carcinoma, triple-negative breast cancer, small cell lung cancer, and pancreatic cancer. Summit’s global studies include HARMONi, HARMONi-3 and HARMONi-7 in NSCLC, while HARMONi-GI3 is evaluating ivonescimab in metastatic colorectal cancer and HARMONi-GU1 is assessing the therapy with enfortumab vedotin in previously untreated metastatic urothelial carcinoma. Ivonescimab has already demonstrated positive results in several Phase III programs conducted in China. The company reports statistically significant overall survival benefits in HARMONi-A, HARMONi-2 and HARMONi-6 in NSCLC, as well as in HARMONi-GI1 in advanced biliary tract cancer. Akeso received marketing authorization in China for ivonescimab based on HARMONi-2 results in 2025. However, the therapy remains investigational in Summit’s license territories, including the United States and Europe. Summit has also submitted a Biologics License Application (BLA) to the U.S. FDA for another ivonescimab-based NSCLC regimen, with the application accepted for filing in January 2026 and a target PDUFA date of November 14, 2026. The latest HARMONi-2 OS findings therefore add another important clinical development milestone for ivonescimab as Summit and Akeso continue evaluating the next-generation immuno-oncology candidate across multiple tumor types and treatment settings.

Source: Summit Therapeutics, Akeso press release