FDA Receives BLA for Ivonescimab Combo in Advanced/Metastatic EGFR+ NSCLC

Developers have submitted a biologics license application (BLA) for second-line or later ivonescimab plus chemotherapy for patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR mutations, according to a press release from Summit Therapeutics Inc.¹

A novel, first-in-class bispecific antibody designed to target PD-1 and block VEGF, developers engineered ivonescimab to possess a tetravalent structure that may exhibit higher avidity in the tumor microenvironment. Between the agent’s design and a half-life of 6 to 7 days following an initial dose, investigators hypothesize that ivonescimab may improve upon efficacy thresholds, toxicities, and safety profiles related to previously approved agents that target PD1 or VEGF.

“This BLA submission, the first for ivonescimab, marks a critical milestone for Summit, our global clinical development plan, and the many patients with [EGFR-mutated] NSCLC in need of better therapeutics options,” Robert W. Duggan and Maky Zanganeh, DDS, MBA, co-chief executive officers at Summit, stated in the press release.¹ “As we continue to support and expand ivonescimab’s rapid development via our growing set of global phase 3 trials and clinical collaborations, we look forward to the potential first US approval for ivonescimab in this difficult to treat setting.”

Supporting data for the BLA came from the phase 3 HARMONi trial (NCT06396065) evaluating ivonescimab in combination with platinum-containing chemotherapy vs placebo/chemotherapy among patients with EGFR-mutated advanced or metastatic NSCLC who progressed on prior treatment with a third-generation EGFR tyrosine kinase inhibitor. Investigators previously presented detailed results from the HARMONi trial in September 2025 at the IASLC 2025 World Conference on Lung Cancer.²

Based on independent radiology review committee assessment, the median progression-free survival (PFS) was 6.8 months with ivonescimab plus chemotherapy vs 4.4 months with placebo plus chemotherapy (HR, 0.52; 95% CI, 0.41-0.66; P <.0001). In each respective arm, the 6-month PFS rates were 54.0% vs 34.7%, and the 12-month rates were 25.4% vs 8.3%. Investigator evaluation showed a consistent PFS benefit in the ivonescimab arm (HR, 0.58; 95% CI, 0.45-0.73).

Additional data showed a median overall survival (OS) of 16.8 months in the ivonescimab arm and 14.0 months in the placebo arm (HR, 0.79; 95% CI, 0.62-1.01; P = .0570). The ivonescimab regimen produced an overall response rate (ORR) of 45% and a disease control rate (DCR) of 84%; these rates were 34% and 73%, respectively, in the placebo arm. The median duration of response (DOR) was 7.6 months (95% CI, 5.5-10.6) in the experimental arm and 4.2 months (95% CI, 2.9-4.7) in the placebo arm.

Any-grade adverse effects (AEs) occurred in 95.0% of the ivonescimab arm and 93.1% of the placebo arm; grade 3 or higher toxicities were reported in 50.0% and 42.2%, respectively. The most common AEs of any grade in each arm included anemia (49.1% vs 56.4%), white blood cell count decreases (45.0% vs 44.0%), and neutrophil count decreases (42.7% vs 42.2%).

In the global phase 3 trial, patients with locally advanced or metastatic NSCLC harboring EGFR sensitizing mutations were randomly assigned 1:1 to receive ivonescimab at 20 mg/kg every 3 weeks (n = 219) or matched placebo (N = 219) plus chemotherapy. All patients received carboplatin area under the curve 5 every 3 weeks for 4 cycles plus pemetrexed at 500 mg/m² every 3 weeks. The trial’s primary end points were OS and PFS per IRRC evaluation based on RECIST v1.1 guidelines. Secondary end points included ORR, DOR, and safety and tolerability.

References

1. 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 13, 2026. https://tinyurl.com/2s9kjmrb
2. 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.