Summit Therapeutics Pursues FDA Application for Ivonescimab Despite Mixed Clinical Results

Summit Therapeutics is moving forward with plans to submit a regulatory application for ivonescimab, its PD-1/VEGF inhibitor antibody, to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2025. This decision comes despite the drug's failure to demonstrate a significant overall survival benefit in certain non-small cell lung cancer (NSCLC) patients during its Phase III HARMONi study.

Pushing Ahead with FDA Application

During Summit's Q3 earnings call, Urte Gayko, the company's chief regulatory, quality and pharmacovigilance officer, acknowledged that the FDA had previously indicated that a significant overall survival (OS) benefit would be necessary to support ivonescimab's application. However, Gayko expressed confidence in the strength of the overall data package, stating, "We do think that the totality of our data from a combination of efficacy and safety is a strong package."

The company plans to submit a biologics license application for ivonescimab as a second-line treatment for EGFR-mutated NSCLC. Summit's decision to proceed with the filing is based on the consistency of data between Western and Asian patients in long-term follow-up studies. Gayko confirmed that Summit is in close contact with the FDA regarding the application process.

Clinical Trial Results and Data Analysis

The Phase III HARMONi study, which forms the basis of Summit's FDA application, focused on patients with locally advanced or metastatic NSCLC who are positive for EGFR activation mutations and have undergone prior treatment with a tyrosine kinase inhibitor. The study compared ivonescimab plus chemotherapy against placebo plus chemotherapy.

Interim data released in May showed that the ivonescimab regimen met its progression-free survival (PFS) endpoint, resulting in a 48% reduction in the risk of disease progression or death. However, the drug fell short of its overall survival endpoint, showing only a 21% reduction in the risk of all-cause death, which did not reach statistical significance.

A detailed readout released last month provided additional insights, demonstrating broadly consistent survival benefits across different geographical regions. Asian patients receiving ivonescimab showed a 24% OS benefit, while those from North America and European countries saw a 16% decrease in the risk of death. Across all patient groups, ivonescimab reduced the risk of disease progression or death by 43% compared to the placebo group.

Additional Clinical Developments

Summit and its partner Akeso recently presented new data at the 2025 European Society for Medical Oncology (ESMO) from the Phase III HARMONi-6 study. This trial evaluated ivonescimab as a first-line treatment for patients with advanced NSCLC and showed significant improvements in progression-free survival. However, overall survival data for this study is not yet available.

Despite the mixed results, some industry analysts remain optimistic about ivonescimab's potential. Truist Securities noted in a report to investors that there is "a lot to sing about" for the drug, citing favorable feedback from the FDA and physician interest in using ivonescimab for EGFR-mutated NSCLC patients.