Summit Therapeutics has said that its partner Akeso reported a statistically significant overall survival benefit for ivonescimab over pembrolizumab in patients with PD-L1-positive advanced non-small cell lung cancer, adding another positive late-stage result to the drug’s development program.
The result comes from the Phase III HARMONi-2 trial, a randomized, double-blind study conducted by Akeso in China that compared ivonescimab monotherapy with pembrolizumab monotherapy in patients with locally advanced or metastatic NSCLC whose tumors expressed PD-L1.
Overall survival was a prespecified secondary endpoint. Akeso said ivonescimab produced a statistically significant improvement over pembrolizumab in the preplanned analysis. Detailed results are expected to be presented at an upcoming medical conference.
The latest finding builds on HARMONi-2’s earlier success. In its primary analysis, ivonescimab significantly improved progression-free survival, with an independent radiologic review committee-assessed hazard ratio of 0.51 versus pembrolizumab.
The progression-free survival benefit was reported across key clinical subgroups, including patients with both low and high PD-L1 expression and those with squamous and non-squamous disease.
Akeso received marketing authorization for ivonescimab from China’s National Medical Products Administration in April 2025 based on HARMONi-2 results.
The situation is different in the United States and Europe. Ivonescimab, known as SMT112 in Summit’s licensing territories, remains investigational and has not been approved by regulatory authorities in those markets.
The drug is designed to combine two established cancer-treatment mechanisms in a single bispecific antibody: blocking PD-1 to stimulate an immune response while also targeting VEGF, a pathway involved in tumor blood-vessel formation.
Summit says the molecule’s engineered structure is intended to promote cooperative binding to its targets, with stronger affinity for PD-1 in the presence of VEGF. The company believes this could help concentrate the drug’s activity in the tumor microenvironment.
HARMONi-2 is the latest in a string of positive Phase III results for ivonescimab.
According to Summit, five Phase III ivonescimab studies have reported results to date, and all five have produced positive data. Four involve NSCLC, while one focuses on biliary tract cancer.
Akeso has reported statistically significant overall survival benefits in three China-based Phase III NSCLC studies — HARMONi-A, HARMONi-2 and HARMONi-6 — as well as in the Phase III HARMONi-GI1 study in advanced biliary tract cancer.
Summit is pursuing the drug across an expanding global clinical program. The company currently has five sponsored global Phase III studies, while additional trials are being conducted by Akeso in China and by the cooperative group GORTEC.
Summit’s most advanced U.S. regulatory effort centers on HARMONi, a Phase III trial testing ivonescimab plus chemotherapy against placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC previously treated with a third-generation EGFR tyrosine kinase inhibitor such as osimertinib.
The company submitted a Biologics License Application to the U.S. Food and Drug Administration, which accepted the application for filing in January 2026. The current target action date under the Prescription Drug User Fee Act is November 14, 2026.
Summit is also testing ivonescimab in first-line metastatic NSCLC regardless of PD-L1 expression in HARMONi-3 and in patients with high PD-L1 expression in the Phase III HARMONi-7 study.
Beyond lung cancer, the company has expanded development into colorectal cancer with HARMONi-GI3 and into urothelial carcinoma with HARMONi-GU1, a Phase II/III study combining ivonescimab with enfortumab vedotin.
Akeso is separately studying the drug in additional cancers, including triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer and pancreatic cancer.
More than 4,000 patients have received ivonescimab in clinical studies globally, according to Akeso, while more than 70,000 patients have been treated in commercial use in China.
