Summit Therapeutics faces potential regulatory challenges for its lung cancer drug ivonescimab after Phase III trial data revealed significant geographical disparities in efficacy outcomes. The bispecific antibody demonstrated markedly better performance in Asian patients compared to those from North America and Europe, potentially complicating the company's path to U.S. and European approval.
Regional Efficacy Variations Emerge
Data from the Phase III HARMONi trial, presented at the Presidential Symposium at the 2025 World Conference on Lung Cancer, showed that ivonescimab combined with chemotherapy produced a median overall survival of 16.8 months in Western patients versus 14 months in the placebo plus chemotherapy control group. This 22% benefit fell just under statistical significance with a p-value of 0.0332.
The geographical disparities were particularly pronounced in progression-free survival outcomes. Patients from China treated with ivonescimab and chemotherapy experienced a 45% reduction in the risk of tumor progression compared to chemotherapy and placebo. However, participants from Western countries saw only a 33% reduction in tumor progression risk—a result that failed to reach statistical significance.
Survival Benefits Show Geographic Patterns
When analyzing overall survival by region, ivonescimab demonstrated a 24% overall survival benefit in Asian patients, while the Western subgroup comprising patients from North America and European countries experienced a 16% reduction in the risk of death. Notably, in North American patients specifically, median overall survival had not yet been reached at the time of data readout, with the ivonescimab regimen showing a 30% overall survival benefit.
The HARMONi trial enrolled patients with EGFR-mutant non-small cell lung cancer with locally advanced or metastatic disease. Despite the regional variations in overall survival, Summit reported that ivonescimab plus chemotherapy cut the risk of disease progression or death by 43% compared to the placebo arm when analyzing Western and Asian patients with at least six months of follow-up.
Regulatory Hurdles Mount
The geographical inconsistencies present significant regulatory challenges for Summit Therapeutics. In May, the company announced that ivonescimab had missed its overall survival target in the trial, and the FDA has since indicated that "a statistically significant overall survival benefit is necessary to support marketing authorization" in the United States.
Truist Securities analysts noted in an investor report that "the regulatory path for Ivonescimab in EGFR-mutant lung cancer is uncertain, and reliant on an act of leniency by the FDA." While Summit had previously stated its intention to file a Biologics License Application for ivonescimab, the company's recent communications have been more cautious, with co-CEO Robert Duggan only indicating that the late-stage data suggest potential benefits for patients across the globe, "including the United States."
Clinical Trial Design and Endpoints
The Phase III HARMONi study evaluated ivonescimab as a bispecific antibody treatment in combination with chemotherapy against a control arm of placebo plus chemotherapy. Progression-free survival serves as a co-primary endpoint of the study, and Summit maintains that the 43% reduction in disease progression or death risk demonstrates the "consistent benefit" of ivonescimab across different patient groups.
