FDA Accepts Ivonescimab Application for EGFR Lung Cancer

The U.S. Food and Drug Administration (FDA) has accepted for filing a biologics license application from Summit Therapeutics seeking approval of ivonescimab in combination with chemotherapy for patients with epidermal growth factor receptor-mutated (EGFR) locally advanced or metastatic non-squamous non-small cell lung cancer whose disease progressed after tyrosine kinase inhibitor therapy, a step that starts a formal review process with a target decision date of Nov. 14, 2026.

The application is based on results from the global phase 3 HARMONi clinical trial and addresses a setting where Summit reports a significant unmet need, with more than 14,000 patients in the United States potentially eligible for treatment each year.

Main data that support the findings: What evidence supported the FDA filing?

The FDA filing is supported by overall results from the phase 3 HARMONi trial, which evaluated ivonescimab plus platinum-doublet chemotherapy compared with placebo plus platinum-doublet chemotherapy. The study enrolled patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who had previously been treated with a third-generation EGFR tyrosine kinase inhibitor.

According to a press release, detailed results from the HARMONi study were provided in September 2025 and formed the basis of the biologics license application submission. While specific numerical outcomes were not included in the announcement, the acceptance of the application indicates the FDA determined the submission was sufficiently complete to permit a full review.

The agency stated it plans to conduct a complete review in line with its draft guidance and good review management principles and practices for new drug applications and biologics license applications. This process is expected to include mid-cycle and wrap-up meetings and the discussion of proposed labeling, assuming no major deficiencies are identified during the review.

Ivonescimab has also been evaluated across a broad development program. More than 4,000 patients have been treated with ivonescimab in clinical studies globally. When including patients treated in a commercial setting in China, more than 60,000 patients have received the therapy, as noted by Akeso, the company that engineered the drug.

Trial details: Who was studied and how was the trial designed?

HARMONi is a global phase 3 clinical trial designed to evaluate ivonescimab in combination with chemotherapy compared with placebo plus chemotherapy. The study enrolled patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer whose cancer had progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor, such as Tagrisso (osimertinib).

The trial is part of a broader phase 3 development program for ivonescimab. Summit began enrolling patients in HARMONi and another global study, HARMONi-3, in 2023. Additional trials include HARMONi-7, which began enrolling patients in 2025, and HARMONi-GI3, which expanded development into colorectal cancer later that same year.

Ivonescimab is a bispecific antibody designed to block both PD-1 and VEGF within a single molecule. According to the company, the therapy was engineered to have cooperative binding to both targets and a tetravalent structure with four binding sites. The intent of this design is to increase binding strength within the tumor microenvironment compared with normal tissue.

The drug has a reported half-life of six to seven days after the first dose, increasing to approximately 10 days at steady state dosing. Ivonescimab is currently being studied in 14 phase 3 clinical trials that are ongoing or completed, including studies in lung cancer and other tumor types.

Safety: What is known about safety and regulatory status?

Ivonescimab is an investigational therapy and is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. The drug received fast track designation from the FDA for the HARMONi clinical trial setting, a program intended to facilitate development and review of therapies for serious conditions.

The press release states that safety profiles across multiple studies have been manageable, including in randomized phase 3 trials conducted by Akeso in China. However, specific safety data or rates of side effects from the HARMONi trial were not detailed in the announcement.

Reference

1. “HARMONi phase 3 trial of ivonescimab in EGFR-mutated non-small cell lung cancer” News Release. iScience. Jan 29, 2026

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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