Peer-reviewed results from the global Phase III HARMONi trial have confirmed a significant PFS benefit for ivonescimab in EGFR-mutated NSCLC, but the study's primary overall survival (OS) analysis remained non-significant ahead of a US FDA decision due November 14, 2026. The primary analysis of the trial data was published in The Lancet Oncology, while Summit Therapeutics Inc.'s (Nasdaq: SMMT) press release plans to present updated OS data at the World Conference on Lung Cancer (WCLC 2026) on September 15, 2026.
HARMONi is a randomized, double-blind, placebo-controlled Phase III trial enrolling patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose disease progressed after a third-generation EGFR tyrosine kinase inhibitor (TKI). The study ran across 114 centers in Asia, Europe, and North America. At the primary analysis, ivonescimab plus platinum-doublet chemotherapy produced a median progression-free survival (PFS) of 6.8 months versus 4.4 months with placebo plus chemotherapy, a hazard ratio of 0.52 (95% CI: 0.41–0.66; p<0.0001) assessed by independent radiographic review. The PFS benefit was consistent across preplanned subgroups. At the time of the primary OS analysis, the combination showed a positive OS trend that did not reach statistical significance. Treatment-related grade 3–5 hemorrhage events occurred in fewer than 1% of patients in the ivonescimab arm, consistent with prior clinical experience, Summit said.
Ivonescimab simultaneously blocks PD-1 and vascular endothelial growth factor (VEGF) through a single tetravalent bispecific antibody engineered by China-based Akeso Inc. (HKEX: 9926.HK). The molecule is designed to preferentially accumulate in the tumor microenvironment, where both PD-1 and VEGF are more highly expressed than in normal tissue. Summit holds commercialization rights in North America, South America, Europe, the Middle East, Africa, and Japan; Akeso retains rights elsewhere, including China, where ivonescimab was first approved in May 2024 for EGFR-TKI-resistant non-squamous NSCLC.
The post-third-generation TKI setting has historically resisted immunotherapy. Prior Phase III studies of PD-1 monoclonal antibodies failed to show PFS or OS benefit in this population, making HARMONi's statistically significant PFS result the first for an immunotherapy-based regimen in a global trial of this kind, Summit said. An updated OS analysis based on a June 2026 data cut showed a continued positive OS trend, with western patients achieving an OS hazard ratio of 0.76, consistent with the overall study population. That data will be presented at WCLC 2026. The HARMONi-A study — a single-region China-based predecessor trial in a similar population — demonstrated a statistically significant OS benefit (HR 0.74; p=0.019), providing supportive context for the global dataset.
Summit proceeded with its BLA submission based on the PFS result and the positive OS trend, citing the absence of any FDA-approved regimen with demonstrated OS benefit in this patient population and the consistency of results between Asian and western cohorts. The PDUFA goal action date is November 14, 2026.