An updated overall survival (OS) analysis from the global phase 3 HARMONi trial (NCT05899608) showed that ivonescimab plus platinum-doublet chemotherapy continued to produce a consistent, favorable survival trend compared with placebo plus chemotherapy in both Western and Asian patients with EGFR-mutated non–small cell lung cancer (NSCLC), according to a news release from the developer, Summit Therapeutics Inc.1
The trial enrolled patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who had previously progressed on a third-generation EGFR tyrosine kinase inhibitor (TKI). The study’s primary analysis had already demonstrated a statistically significant benefit in progression-free survival (PFS), one of the trial’s 2 primary end points along with OS.
In the primary OS analysis, conducted in April 2025, ivonescimab plus chemotherapy showed a positive trend that did not reach statistical significance, with a hazard ratio (HR) of 0.79 (95% CI, 0.62-1.01; P = .057). The median OS was 16.8 months with ivonescimab plus chemotherapy compared with 14.0 months with placebo plus chemotherapy. At that time, Western patients had a median follow-up of only 9.2 months, shorter than the median OS itself, while Asian patients had already accrued 32.7 months of follow-up.
A subsequent analysis in September 2025, incorporating additional follow-up of Western patients to 13.7 months, produced an HR of 0.78 (95% CI, 0.62-0.98; nominal P = .0332), consistent with the primary analysis; the median OS in both arms was unchanged. A further analysis with a June 2026 data cutoff, by which point most Western patients had discontinued treatment or completed 2 years on study, showed an HR of 0.76 in both the intention-to-treat population and the Western patient subgroup specifically, with Western follow-up now extended to 23.2 months.
Across the 3 data cutoffs, the HR for the Western subgroup improved from 0.98 to 0.84 to 0.76, bringing the magnitude of benefit in line with that observed in Asian patients, who had longer follow-up at the time of the primary analysis. More detailed results from the June 2026 cutoff, including updated median OS and confidence intervals, are expected to be presented at an upcoming medical meeting; the data have already been shared with the FDA. Investigators reported no new safety signals, describing ivonescimab’s safety profile in this cutoff as acceptable and manageable and consistent with prior phase 3 findings.
“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,” Maky Zanganeh, PhD, president and co-chief executive officer (CEO)of Summit Therapeutics, said in the release.1 Robert W. Duggan, chairman and co-CEO of Summit, added that with 4 positive phase 3 studies and demonstrated consistency between Asian and Western populations on the OS endpoint, the company believes ivonescimab could represent “the next generation of solid tumor cancer therapy.”
Ivonescimab is a bispecific antibody that combines PD-1 blockade with anti-VEGF activity in a single tetravalent molecule designed for cooperative, higher-affinity binding to PD-1 in the presence of VEGF within the tumor microenvironment. Summit’s biologics license application (BLA) for ivonescimab, based on the HARMONi trial, was accepted for filing by the FDA in January 2026 and carries a Prescription Drug User Fee Act goal date of November 14, 2026. The drug is already approved for marketing in China but remains investigational in the US and Europe.
Beyond HARMONi, ivonescimab development includes several other ongoing phase 3 studies. Among them is the phase 3 HARMONi-3 study (NCT05899608), a randomized, double-blind, multiregional trial comparing ivonescimab plus chemotherapy with pembrolizumab plus chemotherapy in patients with first-line metastatic squamous or non-squamous NSCLC, regardless of PD-L1 expression, with the 2 histologies evaluated as separately powered cohorts.2 Other studies in the program include the phase 3 HARMONi-7 trial (NCT06767514), comparing ivonescimab monotherapy with pembrolizumab monotherapy in first-line NSCLC with high PD-L1 expression, and the phase 3 HARMONi-GI3 trial (NCT07228832), evaluating ivonescimab in metastatic colorectal cancer.
References
1. Ivonescimab plus chemotherapy shows consistent, favorable overall survival results in Western and Asian patients in updated analysis from global phase III HARMONi study. News release. Summit Therapeutics Inc. July 22, 2026. Accessed July 22, 2026. https://tinyurl.com/yft6xjww
2. A randomized, double-blind, multiregional phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic non-small cell lung cancer (HARMONi-3). ClinicalTrials.gov. Updated April 30, 2026. Accessed July 22, 2026. https://tinyurl.com/yc6d2zyu
