Ivonescimab elicited better overall survival in Asian patients with non-small cell lung cancer than in those from North America and European countries, in Western countries narrowly missing the statistical significance threshold the FDA is seeking.
Summit Therapeutics’ closely watched cancer therapy ivonescimab could be tripped up by geographical inconsistencies in its efficacy, with detailed Phase III non-small cell lung cancer data pointing to better survival outcomes in Asian patients versus those in Western populations.
According to data from the Phase III HARMONi trial, Summit’s bispecific antibody, when combined with chemotherapy, resulted in a median overall survival of 16.8 months in Western patients, versus 14 months in comparators on placebo plus chemotherapy. The effect, a 22% benefit, fell just under statistical significance with a p-value of 0.0332, according to the company’s announcement. Cutoff for these findings was this month. The data were presented at the Presidential Symposium at the 2025 World Conference on Lung Cancer on Sunday.
When disaggregating according to region, ivonescimab appears to work better in Asian patients, resulting in a 24% overall survival benefit, whereas those in the Western subgroup—comprising patients from North America and European countries—saw a 16% drop in the risk of death. Meanwhile, in North American patients specifically, median overall survival had not yet been reached at the time of read out. Overall survival benefit was 30% in favor of the ivonescimab regimen. Summit did not provide statistical analyses for any of these figures.
HARMONi enrolled NSCLC patients carrying EGFR mutations with locally advanced or metastatic disease. In May, Summit announced that ivonescimab had missed its overall survival target in the trial, raising questions about the asset’s approval prospects in the U.S.
“The bottom line is that the regulatory path for Ivonescimab in EGFR-mutant lung cancer is uncertain, and reliant on an act of leniency by the FDA,” Truist Securities wrote in a note to investors on Monday morning.
Indeed, alongside its topline readout, the biotech said it had been told by the FDA that “a statistically significant overall survival benefit is necessary to support marketing authorization” in the U.S.
Still, the company at the time maintained that it “intends to file a Biologics License Application” for ivonescimab. Summit did not make such an explicit announcement in its news release on Sunday, with co-CEO Robert Duggan only saying that the late-stage data indicate the potential benefits of ivonescimab to patients across the globe, “including the United States.”
Summit on Sunday also provided progression-free survival data for ivonescimab plus chemotherapy. Compared with a corresponding placebo arm, the investigational regimen cut the risk of disease progression or death by 43%. This analysis includes Western and Asian patients with at least six months of follow-up, which according to Summit demonstrates the “consistent benefit” of ivonescimab across different patient groups. PFS is a co-primary endpoint of the Phase III study.
Ivonescimab is an investigational antibody that works by blocking both the PD-1 and VEGF pathways, a mechanism that prevents the tumor from evading immune response and establishing new blood vessels to sustain itself. The asset became the face of this emerging approach against cancer after it bested Keytruda in the Phase III HARMONi-2 trial, demonstrating significantly better PFS in patients with advanced NSCLC.
