Summit Therapeutics and Akeso are answering questions raised about ivonescimab’s ability to translate to Western populations, though the partners have yet to share if the new findings are statistically significant.
After two years of follow-up, Summit Therapeutics and China partner Akeso’s PD-1/ VEGF-targeting antibody ivonescimab is proving its prolonged impact on overall survival across geographies.
New data posted Wednesday reveal that a subgroup of Western patients achieved an overall survival (OS) hazard ratio (HR) of 0.76 at 23.2 months—translating to a 24% lower risk of death compared to patients receiving standard of care. While Summit didn’t share whether the finding was statistically significant, it is similar to the result for trial participants in China, which showed an OS HR of 0.74, or a 26% reduction, at 32.5 months.
The findings come from the global Phase 3 HARMONi trial evaluating Summit and Akeso’s investigational bispecific antibody alongside chemotherapy. The study enrolled patients with endothelial growth factor receptor (EGFR)-mutated, advanced non-squamous non-small cell lung cancer (NSCLC) who had previously received a third-generation EGFR tyrosine kinase inhibitor.
The fresh findings paint a clearer picture of ivonescimab’s impact for Western patients. The partners first made a splash in 2024 when data from the Phase 3 HARMONi-2 trial conducted in China showed the drug was 49% more effective than Merck’s blockbuster Keytruda at reducing risk of disease progression or death. Early on, Summit had only emphasized that global OS trended positively. Then, last September, an additional analysis demonstrated a hazard ratio of 0.78 for Western patients at 13.7 months, a nominally positive finding that wasn’t declared statistically significant.
“The risk that China data would not translate has been a lingering bear argument,” Stifel analysts wrote in a Wednesday note. But the newest data is “a strong counter to that pushback,” Stifel said.
Wednesday’s results also bolster the theory that more time reveals ivonescimab’s “vaccinal effect,” creating an immune memory against the cancer. This means a longer follow-up should demonstrate a stronger hazard ratio. “That is exactly what this analysis shows,” Stifel wrote.
“Unlike legacy anti-VEGFs that are known to only right-shift the PFS curve without OS benefit, ivonescimab delivers better immunotherapy, and that shows up in the tail of the OS curve,” the analysts explained.
Stifel is “encouraged but not surprised” by the new findings, adding that the result “reduces an already-limited” regulatory risk in second-line EGFR-mutated NSCLC. But Stifel never viewed ivonescimab’s chances in the indication as holding meaningful regulatory risk given that others—such as Johnson and Johnson’s Rybrevant—have secured approval using a positive OS trend without formal statistical significance.
“Bears can still point to the lack of explicit statistical-significance language, but in our view the more relevant FDA question is whether the global data are consistent, and this update directly addresses that concern,” Stifel wrote.
Summit has provided the FDA with the updated analysis as it continues to advance its Biologics Licensing Application (BLA) filing forward. The submission was launched at the beginning of this year, with a decision expected by Nov. 14.
Stifel believes the newest data also derisks the HR data expected later this year from HARMONi-3, which is testing an ivonescimab injection as a first-line treatment for metastatic NSCLC.
