Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non–Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial
Mené en Chine sur 322 patients atteints d'un cancer du poumon non épidermoïde non à petites cellules présentant un variant du gène EGFR et de stade localement avancé ou métastatique (âge médian : 59,4 ans ; durée médiane de suivi : 32,5 mois), cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout d'ivonescimab à une chimiothérapie combinant pémétrexed et carboplatine
Importance : Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non–small cell lung cancer (NSCLC) who have disease progression after prior EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options, creating a need for more effective subsequent therapies.
Objective : To provide final overall results of a trial assessing whether adding ivonescimab (a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor) to chemotherapy improves overall survival in this population.
Design, Setting, and Participants : Randomized, double-blind, placebo-controlled phase 3 trial conducted at 55 sites in China. From January 25 to November 2, 2022, a total of 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025.
Interventions : Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n = 161) or placebo (n = 161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy.
Main Outcomes and Measures : This final results report focuses on overall survival, the key secondary end point, tested in a hierarchical manner (the primary end point was progression-free survival assessed by an independent radiology review committee).
Results : The 322 enrolled patients had a median age of 59.4 years, and 51.6% were female. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved overall survival compared with chemotherapy alone (median survival, 16.8 months vs 14.1 months; stratified hazard ratio, 0.74; 95% CI, 0.58-0.95; P = .02). The absolute difference in median overall survival was 2.7 months. Estimated 30-month survival rates were 29.1% (95% CI, 22.1%-36.4%) with ivonescimab and 18.4% (95% CI, 12.8%-24.8%) with placebo. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively.
Conclusions and Relevance : Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy.
JAMA , résumé, 2026