Akeso's bispecific antibody ivonescimab delivered a statistically significant overall survival improvement over Merck's Keytruda in the HARMONi-2 study, marking the fourth Phase III trial where the drug showed benefit on both survival and progression. The readout bolsters Summit Therapeutics' regulatory push, with an FDA decision on a related lung-cancer filing due Nov. 14.
Ivonescimab beat pembrolizumab on overall survival, a fourth Phase III study to show the drug's dual survival and progression benefit.
"These results further reinforce the clinical value of ivonescimab in the treatment of lung cancer," Yu Xia, founder, chairwoman and chief executive officer of Akeso, said in a statement.
The pre-specified interim analysis of overall survival, a secondary endpoint in the HARMONi-2 study, met its key secondary endpoint with a statistically significant and clinically meaningful improvement over pembrolizumab (Keytruda), Akeso said Sept. 2. The trial enrolled patients with locally advanced or metastatic non-small cell lung cancer whose tumors express PD-L1 at a tumor proportion score of at least 1 percent. In the primary analysis announced in May 2024, ivonescimab cut the risk of disease progression by 49 percent versus pembrolizumab, with a hazard ratio of 0.51 and median progression-free survival of 11.14 months versus 5.82 months.
The result hands Summit Therapeutics, which holds rights to ivonescimab outside China, a second survival win to take to US regulators. Summit's application for the drug in EGFR-mutated lung cancer was accepted by the US Food and Drug Administration in January, with a decision due Nov. 14.
Ivonescimab is a first-in-class bispecific antibody that blocks PD-1 and vascular endothelial growth factor in one molecule, pairing checkpoint inhibition with anti-angiogenesis. Its design gives it higher affinity for PD-1 when VEGF is present, a property intended to concentrate the drug in tumor tissue. China's National Medical Products Administration approved the drug for first-line PD-L1-positive non-small cell lung cancer in April 2025 based on the HARMONi-2 progression-free survival data.
The survival result extends a run of wins for the drug. Akeso has reported statistically significant overall survival benefits in three China-based Phase III studies in lung cancer — HARMONi-A, HARMONi-2 and HARMONi-6 — as well as in the HARMONi-GI1 trial in biliary tract cancer. More than 4,000 patients have been treated with ivonescimab in clinical studies globally, and over 70,000 in commercial use in China, according to Akeso.
The outcome pressures Merck, whose Keytruda is the standard of care in first-line lung cancer and one of the world's best-selling drugs. A head-to-head survival defeat in that setting raises the competitive risk to the franchise as rivals including BioNTech's pumitamig and Pfizer's PF-08634404 advance similar bispecific antibodies.
Summit is running five global Phase III studies of ivonescimab, including HARMONi-3 and HARMONi-7 in first-line non-small cell lung cancer, and expanded into colorectal and urothelial cancer in 2025 and 2026. Detailed HARMONi-2 survival data are scheduled for presentation at an upcoming medical conference. Investors will watch the FDA decision on the EGFR-mutated indication on Nov. 14 as the next event for Summit shares.
This article is for informational purposes only and does not constitute investment advice.
