In May, Summit released early data from the Phase III HARMONi study showing that while the PD-1/VEGF inhibitor resulted in significant progression-free survival improvements, it fell short of the overall survival bar.
Even after failing to demonstrate a significant overall survival benefit in certain patients with non-small cell lung cancer, Summit Therapeutics is pushing through with a regulatory application for its Akeso-partnered PD-1/VEGF inhibitor antibody ivonescimab, with a filing scheduled for the fourth quarter.
Speaking to investors during the company’s Q3 earnings call on Monday, Urte Gayko, the company’s chief regulatory, quality and pharmacovigilance officer, acknowledged that the FDA has previously told the company a significant OS benefit is necessary to support ivonescimab’s application. Still, “We do think that the totality of our data from a combination of efficacy and safety is a strong package,” she said.
When an analyst brought up the possibility of delaying the biologics license application until after an upcoming readout in an adjacent indication that could potentially lead to a stronger submission, Gayko noted that Summit instead intends to use these forthcoming data to back another application.
“Our thinking is that each indication will have its own submission,” she said. “This particular package is ready now. We have shown consistency in the data with our long-term follow-up between the Western patients and the Asian patients. We think this is the right opportunity.”
The application in question will be for second-line EGFR-mutated NSCLC.
Truist Securities was positive regarding the filing plans. Writing to investors on Monday, analysts said there is “a lot to sing about” for ivonescimab, noting that in talks with Summit, management has indicated they have “received favorable feedback [from FDA] and encouragement to file the data.”
“If the FDA accepts and approves Ivo in 2L+ EGFRm [EGFR mutated] NSCLC, it would be a nice upside,” Truist said. “Our discussions with physicians suggest there is some interest to use Ivo in this population.”
Gayko on the call declined to provide details of Summit’s current discussions with the FDA but confirmed “that we are in close contact with them.”
Summit will back its filing with data from the Phase III HARMONi study, which focused on patients with locally advanced or metastatic NSCLC who are positive for EGFR activation mutations and who have undergone prior treatment with a tyrosine kinase inhibitor. Ivonescimab was given on top of chemotherapy and compared against placebo plus chemotherapy.
Interim data in May showed that the ivonescimab regimen cleared the study’s progression-free survival bar, resulting in a 48% reduction in the risk of disease progression or death. However, the PD-1/VEGF bispecific missed its OS endpoint: the combo treatment lowered the risk of all-cause death by 21%, an effect that fell short of statistical significance.
Summit’s confidence in its data seems to come at least partly from a detailed readout released last month, touting broadly consistent survival benefits in patients from different geographical regions. In Asian patients, for instance, the ivonescimab schedule resulted in a 24% OS, whereas those from North America and European countries saw a 16% decrease in risk of death. Compared to a placebo group, all patients receiving ivonescimab cut their risk of disease progression or death by 43%.
Also on Monday, Summit and Akeso presented new data at the 2025 European Society for Medical Oncology (ESMO) from the Phase III HARMONi-6 study, showing that ivonescimab significantly improved progression-free survival when used as a first-line treatment option for patients with advanced NSCLC. OS data are so far missing from this particular picture.
