Summit公布ivonescimab全球HARMONi三期更新OS分析，西方患者HR改善至0.76并提交FDA

Western Patients Achieved OS HR of 0.76, Consistent with Asian Patients in this Global Phase III Study

MIAMI--(BUSINESS WIRE)--
Summit Therapeutics Inc. (Nasdaq: SMMT) today announced results of an updated overall survival (OS) analysis from the global Phase III HARMONi clinical trial featuring the novel, potential first-in-class investigational bispecific antibody ivonescimab. Ivonescimab plus platinum-doublet chemotherapy in this trial continues to show a positive OS trend and a consistent efficacy and safety profile in Asian and western patients when compared to chemotherapy alone. The HARMONi study is evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with endothelial growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who were previously treated with a third-generation EGFR tyrosine kinase inhibitor (TKI). The study demonstrated a statistically significant benefit in the primary analysis for progression-free survival (PFS), one of the study’s two primary endpoints along with OS. Summit’s Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) is based on the results from the HARMONi trial and has a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026.
In April 2025, the primary OS analysis was performed, whereby ivonescimab in combination with chemotherapy showed a positive trend without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057). Median OS was 16.8 months for those patients administered ivonescimab plus chemotherapy vs. 14.0 months for those receiving placebo plus chemotherapy. At the time of the primary analysis, median follow-up time for western patients was 9.2 months and less than the median OS at the time of the primary analysis.
In September 2025, an additional analysis was performed, whereby the western patients were followed to increase their time on study (Asian patients were included and locked at the time of the primary analysis at a median follow-up time of 32.7 months). This analysis included longer-term follow-up of western patients of 13.7 months. A hazard ratio of 0.78 (95% CI: 0.62 – 0.98; nominal p=0.0332) was observed, consistent with the primary analysis. Median OS remained the same in both arms from the primary analysis.
An additional analysis was performed with a data cut-off date in June 2026, whereby most western patients have now discontinued treatment or completed two years of treatment. The median follow-up time for western patients now is 23.2 months. The cutoff date for Asian patients was consistent with the prior analysis with a median follow-up time of 32.7 months. A hazard ratio of 0.76 was observed in both the full intention-to-treat population and the subgroup of western patients. More detailed data from this analysis are intended to be presented at an upcoming medical meeting. These results have been made available to the FDA.
Global Overall Survival Analyses at Each Data Cut-Off

DCO: Apr 2025
(Primary Analysis)
DCO: Sept 2025
DCO: June 2026*

Ivonescimab + Chemo
Placebo + Chemo
Ivonescimab + Chemo
Placebo + Chemo
Ivonescimab + Chemo
Placebo + Chemo

(n=219)
(n=219)
(n=219)
(n=219)
(n=219)
(n=219)

Hazard Ratio,

ITT
0.79
0.78
0.76

DCO = data cut-off; ITT = intention-to-treat population; mos = months; chemo = chemotherapy

*Note: Additional information, including median OS, confidence intervals for hazard ratios, etc., are intended to be presented at an upcoming medical conference

The hazard ratios for the subgroup of western patients improved from the analysis in April 2025 to the September 2025 and June 2026 analyses with longer-term follow-up of western patients. With longer follow-up, results of western patients are now consistent in terms of the magnitude of OS benefit with those patients enrolled in Asia, who had a longer follow-up at the time of the primary OS analysis.
Western Subgroup of Overall Survival Analyses at Each Data Cut- Off

DCO: Apr 2025
DCO: Sept 2025
DCO : June 2026*

Ivonescimab + Chemo
Placebo + Chemo
Ivonescimab + Chemo
Placebo + Chemo
Ivonescimab + Chemo
Placebo + Chemo

(n=83)
(n=82)
(n=83)
(n=82)
(n=83)
(n=82)

Hazard Ratio,

Western pts
0.98
0.84
0.76

Median

follow-up

time
9.2 months
13.7 months
23.2 months

DCO = data cut-off; ITT = intention-to-treat population; pts = patients; chemo = chemotherapy

*Note: Additional information, including median OS, confidence intervals for hazard ratios, etc., are intended to be presented at an upcoming medical conference

In this most recent analysis, ivonescimab continued to demonstrate an acceptable and manageable safety profile that was consistent with previous Phase III data of ivonescimab plus chemotherapy. No additional safety signals were noted in this current HARMONi data cut.
“The positive results from this latest overall survival analysis in the global HARMONi study continue to support the translation of the therapeutic profile of ivonescimab across the globe, including western patients from North America and Europe,” stated Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit. “We have made this updated analysis available to the FDA as we continue to progress our BLA filing for the potential approval of ivonescimab in the U.S.”
“As we have consistently stated, the ivonescimab clinical trial data across multiple histologies and tumor types have repeatedly portrayed a consistent message: ivonescimab has the opportunity to make a significant difference in the lives of patients with cancer,” added Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. “Ivonescimab continues to demonstrate its potential to increase duration of life with a tolerable safety profile. With four positive Phase III studies and clear consistency between Asian and western patients demonstrated in the global HARMONi study in the gold-standard endpoint of overall survival, we believe that ivonescimab can represent the next generation of solid tumor cancer therapy through its differentiated bispecific design.”
About EGFR-Mutated NSCLC
Lung cancer is the second most commonly diagnosed cancer worldwide and remains the leading cause of cancer-related death globally, with an estimated 2.6 million new cases and 1.9 million deaths in 2024. 1 In the United States, the American Cancer Society estimates that approximately 230,000 new lung cancer cases will be diagnosed and nearly 125,000 deaths from lung cancer will occur in 2026. 2 Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing approximately 80% to 85% of all cases. 1,3
EGFR mutations are among the most common actionable oncogenic drivers in non-squamous NSCLC, occurring in approximately 10-15% of patients in western populations and 40-50% of patients in Asia. 4,5 Activating EGFR mutations can drive tumor growth through aberrant EGFR signaling. 6 EGFR tyrosine kinase inhibitors (TKIs), including third-generation EGFR TKIs, are an important treatment approach for patients with advanced EGFR-mutated NSCLC. 4
Despite advances with EGFR-targeted therapy, most patients with locally advanced or metastatic EGFR-mutated NSCLC eventually experience disease progression after treatment with a third-generation EGFR TKI. 7 In patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC previously treated with a third-generation EGFR TKI, treatment options remain limited, underscoring the need for new therapeutic approaches after progression on EGFR-targeted therapy. 7
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the