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 meet overall survival (OS) endpoints in a recent Phase III trial for non-small cell lung cancer (NSCLC).

HARMONi Trial Results and Regulatory Strategy

The Phase III HARMONi study, which evaluated ivonescimab in combination with chemotherapy for second-line treatment of EGFR-mutated NSCLC, showed significant improvements in progression-free survival (PFS). Patients receiving the ivonescimab regimen experienced a 48% reduction in the risk of disease progression or death compared to those on placebo plus chemotherapy.

However, the trial fell short of its overall survival goal, with only a 21% reduction in the risk of all-cause death—a result that did not reach statistical significance. Despite this setback, Summit's leadership remains confident in the drug's potential. Urte Gayko, Summit's chief regulatory, quality and pharmacovigilance officer, stated during a Q3 earnings call, "We do think that the totality of our data from a combination of efficacy and safety is a strong package."

The company plans to focus its application on second-line EGFR-mutated NSCLC, leveraging data from the HARMONi study. Summit has indicated that they are in close contact with the FDA and have received encouraging feedback regarding their filing plans.

Geographic Variations and Additional Clinical Data

Summit's confidence is bolstered by detailed readouts showing consistent survival benefits across different geographical regions. Asian patients demonstrated a 24% OS benefit, while North American and European patients saw a 16% decrease in the risk of death. Across all regions, ivonescimab reduced the risk of disease progression or death by 43% compared to placebo.

In addition to the HARMONi results, Summit and its partner Akeso presented new data from the Phase III HARMONi-6 study at the 2025 European Society for Medical Oncology (ESMO) conference. This study evaluated ivonescimab as a first-line treatment for advanced NSCLC and showed significant PFS improvements, although OS data are not yet available.

Industry Outlook and Analyst Perspectives

The pharmaceutical industry is closely watching Summit's regulatory strategy. Truist Securities analysts have expressed optimism about the filing plans, noting that there is "a lot to sing about" for ivonescimab. They highlighted that discussions with physicians suggest interest in using the drug for the proposed indication.

However, the path forward remains uncertain. The FDA has previously indicated that a significant OS benefit would be necessary to support ivonescimab's application. Summit's decision to proceed with the filing despite not meeting this criterion represents a bold move in the competitive landscape of cancer therapeutics.

As the fourth quarter of 2025 approaches, the industry will be keenly observing whether Summit's strategy will result in a successful FDA application and potential approval, which could significantly impact treatment options for patients with EGFR-mutated NSCLC.