FDA Accepts BLA for Ivonescimab Regimen in Pretreated EGFR-Mutated NSCLC

The FDA has accepted a biologics license application (BLA) seeking approval for ivonescimab in combination with chemotherapy among patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations following prior tyrosine kinase inhibitors (TKIs), according to a press release from the developer, Summit Therapeutics Inc.¹

The agency has set a Prescription Drug User Fee Act date of November 14, 2026, for approving the ivonescimab-based regimen in this NSCLC population. Developers previously submitted the BLA for the ivonescimab combination earlier in January 2026.²

According to the agency, it will completely review the accepted and filed BLA in alignment with its draft guidance, Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications. The review process will entail mid-cycle and wrap-up meetings as well as proposed labeling for the ivonescimab regimen if the agency identifies no notable deficiencies.

Ivonescimab is a first-in-class bispecific antibody that blocks PD-1 and VEGF simultaneously as part of a single molecule. Developers hypothesize that the agent may uniquely bind to each of its intended targets, with improved affinity to PD-1 when VEGF is involved.

The BLA for ivonescimab-based treatment is backed by data from the phase 3 HARMONi trial (NCT06396065), in which investigators evaluated the novel regimen vs placebo plus chemotherapy among those with EGFR-mutated advanced or metastatic NSCLC and disease progression on prior third-generation EGFR TKIs. At the IASLC 2025 World Conference on Lung Cancer (WCLC), investigators presented detailed findings from the HARMONi trial.³

An independent radiology review committee assessment identified a median progression-free survival (PFS) of 6.8 months among patients who received ivonescimab/chemotherapy vs 4.4 months among those who received placebo/chemotherapy (HR, 0.52; 95% CI, 0.41-0.66; P <.0001). The 6-month PFS rates in each arm were 54.0% vs 34.7%; at 12 months, these rates were 25.4% vs 8.3%. The PFS benefit remained consistent with the ivonescimab regimen according to investigator assessment (HR, 0.58; 95% CI, 0.45-0.73).

“The efficacy of [ivonescimab] was consistent across subgroups, with perhaps more benefit [in patients] with brain metastases,” study investigator Jonathan Goldman, MD, a professor of medicine in the Division of Hematology/Oncology, the director of Clinical Trials in Thoracic Oncology, and the associate director of Early Drug Development at the University of California, Los Angeles, stated in a presentation of the data at WCLC.³

As part of the double-blind, multicenter HARMONi trial, patients were randomly assigned 1:1 to receive ivonescimab (n = 219) or matched placebo (n = 219) in combination with carboplatin and pemetrexed. Patients in the investigational arm received ivonescimab at 20 mg/kg every 3 weeks. All patients received carboplatin at area under the curve 5 every 3 weeks across four 21-day cycles plus pemetrexed at 500 mg/m² every 3 weeks.

The trial’s coprimary end points were PFS and overall survival based on RECIST v1.1 criteria. Secondary end points included overall response rate, duration of response, and safety.

Patients 18 years and older with histologically or cytologically confirmed unresectable locally advanced or metastatic nonsquamous NSCLC harboring EGFR sensitizing mutations were eligible for enrollment on the trial. Other eligibility criteria included having progressive disease on a third-generation EGFR TKI, an ECOG performance status of 0 or 1, and any PD-L1 expression status.

Grade 3 or higher immune-related adverse effects (IRAEs) occurred in 9.6% of patients in the ivonescimab arm compared with 6.0% of those in the placebo arm. The most common IRAEs of any grade in the experimental arm included hypothyroidism (8.3%), hyperthyroidism (4.1%), increased aspartate aminotransferase levels (3.2%), and elevated alanine aminotransferase levels (2.8%).

References

1. Summit Therapeutics announces U.S. FDA acceptance of biologics license application (BLA) seeking approval for ivonescimab in combination with chemotherapy in treatment of patients with EGFRm NSCLC post-TKI therapy. News release. Summit Therapeutics Inc. January 29, 2026. Accessed January 29, 2026. https://tinyurl.com/5fnkka2k
2. Summit Therapeutics announces submission of biologics license application (BLA) to U.S. FDA seeking approval for ivonescimab in combination with chemotherapy in 2L+ treatment of patients with EGFRm NSCLC. News release. Summit Therapeutics Inc. January 12, 2026. Accessed January 29, 2026. https://tinyurl.com/2s9kjmrb
3. Goldman JW, Passaro A, Laskin J, et al. Ivonescimab vs placebo plus chemo, phase 3 in patients with EGFR+ NSCLC progressed with 3rd gen EGFR-TKI treatment: HARMONi. Presented at: International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract 4808.