Ivonescimab Plus Chemotherapy Improves Progression-Free Survival in Patients with EGFR+ NSCLC Following 3rd-Generation EGFR-TKI Therapy
(Barcelona, Spain September 7, 2025, 10:45 a.m. CEST / UTC +2) — Adding ivonescimab, a first-in-class bispecific antibody targeting both PD-1 and VEGF, to chemotherapy significantly prolonged progression-free survival (PFS) compared to chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations whose disease progressed on third-generation EGFR tyrosine kinase inhibitors (TKIs).
Results from the global Phase 3 HARMONi trial were presented today by Jonathan Goldman, UCLA Health, Los Angeles at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC).
The randomized, double-blind, placebo-controlled study enrolled 438 patients worldwide, including 38% from North America and Europe, with a median age of 62 years. Nearly one-quarter (24.7%) had brain metastases at study entry. Patients received ivonescimab (20 mg/kg) or placebo in combination with pemetrexed and carboplatin for four cycles, followed by maintenance therapy.
At the primary analysis (N=345; median follow-up 22.3 months), ivonescimab plus chemotherapy reduced the risk of disease progression or death by 48% compared to chemotherapy alone (HR 0.52; 95% CI: 0.41–0.66; P<0.001). Median PFS was 6.8 months (95% CI: 5.7–7.1) versus 4.4 months (95% CI: 4.1–5.5). The PFS benefit was consistent across all predefined subgroups, including patients with brain metastases (HR 0.34; 95% CI: 0.20–0.57) and Western patients.
At final overall survival (OS) analysis (median follow-up 29.7 months), median OS was 16.8 months with ivonescimab versus 14.0 months with chemotherapy alone (HR 0.79; 95% CI: 0.62–1.01; P=0.0570). The overall response rate was higher in the ivonescimab group (44.7% vs. 34.2%), and intracranial PFS was also improved.
Grade ≥3 treatment-related adverse events occurred in 50.0% of patients receiving ivonescimab and 42.2% in the control arm, most commonly laboratory abnormalities. VEGF-related events, including reversible hypertension and proteinuria, were more frequent with ivonescimab but generally manageable. Treatment-related deaths were rare (1.8% vs. 2.3%).
“Ivonescimab plus chemotherapy provided a clinically meaningful and statistically significant improvement in progression-free survival while maintaining a favorable safety profile in this difficult-to-treat patient population,” said Dr. Goldman. “The benefits were seen regardless of brain metastases status or geographic region and were supported by a positive overall survival trend.”
About the IASLC
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration, and understanding of lung cancer and to help participants implement the latest developments across the globe. The conference covers a wide range of disciplines and unveils several research studies and clinical trial results. For more information, visit https://wclc.iaslc.org/.