Phase 3 HARMONi data show ivonescimab plus chemotherapy significantly improved PFS in EGFR-mutated NSCLC after third-generation EGFR TKI progression.
Written By: Anamika Koshti, Pharm D
Reviewed By: Pharmacally Editorial Team
Summit Therapeutics has announced publication in The Lancet Oncology of primary analysis results from the global Phase 3 HARMONi trial (NCT06396065), which evaluated ivonescimab plus platinum-doublet chemotherapy versus placebo plus platinum-doublet chemotherapy in patients with 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 was conducted at 114 cancer centers and hospitals across Asia, Europe, and North America.
Efficacy Results
At the primary analysis, median progression-free survival (PFS) was 6.8 months with ivonescimab plus chemotherapy versus 4.4 months with placebo plus chemotherapy, corresponding to a hazard ratio of 0.52 (95% CI, 0.41–0.66; P<0.0001). The PFS benefit was consistent across prespecified subgroups. The findings were described by Summit as the first immunotherapy-based regimen to demonstrate a statistically significant and clinically meaningful PFS benefit in a global Phase 3 study in this post-third-generation EGFR TKI setting.
At the primary OS analysis, ivonescimab plus chemotherapy showed a positive trend but did not reach statistical significance. The primary OS analysis reported an OS hazard ratio of 0.79 (95% CI, 0.62–1.01; P=0.057), with median OS of 16.8 months versus 14.0 months. A June 2026 update showed a continued positive OS trend, with an OS hazard ratio of 0.76 in both the full intention-to-treat population and the Western subgroup. Further details are planned for presentation at WCLC 2026.
Safety and Mechanism
The safety profile was described as manageable and consistent with prior clinical experience. Treatment-related grade 3–5 hemorrhage occurred in less than 1% of patients receiving ivonescimab plus chemotherapy in HARMONi.
Ivonescimab, known as SMT112 in Summit’s license territories and AK112 elsewhere, is an investigational tetravalent bispecific antibody designed to block PD-1 and VEGF within a single molecule. Its cooperative binding is designed to increase PD-1 affinity when VEGF is present, with the aim of preferentially directing activity toward the tumor microenvironment. The molecule was engineered by Akeso Inc.
Regulatory Status and Clinical Context
Ivonescimab remains investigational in Summit’s license territories, including the United States and Europe, and received marketing authorization in China in May 2024. The FDA accepted Summit’s BLA for ivonescimab plus chemotherapy in this indication for filing in January 2026 and assigned a PDUFA goal action date of November 14, 2026.
The broader development program includes 16 announced, ongoing, or completed Phase 3 studies across multiple tumor types. For patients with EGFR-mutated NSCLC progressing after a third-generation EGFR TKI, HARMONi provides evidence of a meaningful PFS benefit, but the OS findings remain under follow-up and the therapy is not yet approved in the United States or Europe.
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About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.