Ivonescimab Extends Survival in EGFR-Mutated NSCLC

Adding ivonescimab to chemotherapy improved overall survival (OS) among patients with advanced epidermal growth factor receptor (EGFR)-variant nonsquamous non–small cell lung cancer (NSCLC) whose disease had progressed after EGFR tyrosine kinase inhibitor (TKI) therapy, according to final results from the phase 3 HARMONi-A trial published in JAMA.

The randomized, double-blind, placebo-controlled trial enrolled 322 adults with locally advanced or metastatic disease at 55 sites in China. Participants were assigned 1:1 to receive ivonescimab at 20 mg/kg or placebo. Both groups also received pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy.

After a median follow-up of 32.5 months, median OS was 16.8 months with ivonescimab plus chemotherapy and 14.1 months with chemotherapy alone. The stratified hazard ratio for death was 0.74 (P=.02), corresponding to an absolute difference in median OS of 2.7 months. The estimated 30-month survival rate was 29.1% in the ivonescimab group and 18.4% in the placebo group. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients, respectively.

Overall survival was a hierarchically tested key secondary end point; the trial’s primary end point was progression-free survival assessed by an independent radiology review committee. The investigators concluded that ivonescimab plus chemotherapy produced a statistically significant and clinically meaningful survival benefit with an acceptable safety profile in this post–EGFR-TKI setting.

Ivonescimab is a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor. The drug is not approved in the US. According to Summit Therapeutics, the FDA has accepted a biologics license application for ivonescimab plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC previously treated with a third-generation EGFR TKI. The application is based on results from the separate global phase 3 HARMONi trial. The FDA has set a Prescription Drug User Fee Act goal action date of November 14, 2026.

Sources: HARMONi-A Study Investigators. Bispecific antibody ivonescimab added to chemotherapy in EGFR-variant non–small cell lung cancer: the HARMONi-A randomized clinical trial. JAMA. 2026;336(4):306-314. doi:10.1001/jama.2026.7745

Summit Therapeutics announces U.S. FDA acceptance of biologics license application (BLA) seeking approval for ivonescimab in combination with chemotherapy in treatment of patients with EGFRm NSCLC post-TKI therapy. News release. Summit Therapeutics Inc. January 29, 2026. Summit Therapeutics