Updated HARMONi Analysis Shows Consistent OS Benefit With Ivonescimab in EGFRm Lung Cancer

An updated overall survival (OS) analysis from the global phase 3 HARMONi trial (NCT06396065) shows that ivonescimab, an investigational PD-1/VEGF bispecific antibody, combined with platinum-doublet chemotherapy produced a consistent survival benefit over chemotherapy alone in both Asian and non-Asian patients with EGFR-mutated non–small cell lung cancer (NSCLC).¹

With longer follow-up, the hazard ratio (HR) for death in the non-Asian patient subgroup improved from 0.98 at the time of the primary analysis to 0.76 at the most recent data cutoff, now aligning with the magnitude of benefit previously observed in Asian patients. Summit Therapeutics said these data have been shared with the FDA as it reviews a biologics license application (BLA) for ivonescimab, which carries a Prescription Drug User Fee Act target action date of November 14, 2026.²

HARMONi is a randomized, double-blind, placebo-controlled trial evaluating ivonescimab plus chemotherapy against placebo plus chemotherapy in 438 patients with locally advanced or metastatic, EGFR-mutated, nonsquamous NSCLC who had progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI), such as osimertinib (Tagrisso).¹ Progression-free survival (PFS) and OS were co-primary end points; the trial met its primary end point for PFS, according to Summit.

HARMONi: Previous Data

The company reported OS findings from 3 sequential data cutoffs. At the primary analysis in April 2025, the intention-to-treat (ITT) population showed an OS HR of 0.79 (95% CI, 0.62-1.01; P =.057), with a median OS of 16.8 months for ivonescimab plus chemotherapy vs 14.0 months for placebo plus chemotherapy. At that time, non-Asian patients had a median follow-up of only 9.2 months while Asian patients had already reached a median follow-up of 32.7 months, limiting the ability to detect a benefit uniformly across regions.

A September 2025 update, incorporating 13.7 months of median follow-up in non-Asian patients, showed an ITT HR of 0.78 (95% CI, 0.62-0.98; nominal P =.0332), with median OS unchanged from the primary analysis. The most recent cutoff, in June 2026, corresponded to a median non-Asian follow-up of 23.2 months, by which point most non-Asian patients had discontinued treatment or completed 2 years of therapy. At this cutoff, the ITT HR was 0.76, and the non-Asian subgroup HR was also 0.76, matching the ITT result for the first time. Additional details, including updated median OS values and confidence intervals for the June 2026 analysis, are planned for presentation at an upcoming medical meeting; the figures released to date have not undergone independent peer review.

The safety profile of ivonescimab in this analysis remained consistent with prior phase 3 data, with no new safety signals identified.

Clinical Need

EGFR mutations are detected in an estimated 10% to 15% of patients with nonsquamous NSCLC in non-Asian populations and 40% to 50% of patients in Asia, making the consistency of the treatment effect across these groups clinically relevant for a molecule initially studied predominantly in Asian cohorts.³ Most patients with EGFR-mutated advanced NSCLC eventually progress after third-generation TKI therapy, and treatment options in this setting remain limited.⁴

Ivonescimab is a tetravalent bispecific antibody engineered to bind PD-1 and VEGF cooperatively, with higher affinity for PD-1 in the presence of VEGF. The molecule was first approved in China in May 2024¹ for EGFR-mutated nonsquamous NSCLC after TKI progression, based on the phase 3 HARMONi-A trial (NCT05184712) conducted in China, which showed a statistically significant OS benefit (HR, 0.74; 95% CI, 0.58-0.95) in a final analysis published in JAMA.⁵

REFERENCES

1. Ivonescimab Plus Chemotherapy Shows Consistent, Favorable Overall Survival Results in Western and Asian Patients in Updated Analysis from Global Phase III HARMONi Study. Nes release. Summit Therapeutics. July 22, 2026. Accessed July 22, 2026. https://tinyurl.com/42ybzv8f

2. 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. January 29, 2026. Accessed July 22, 2026. https://tinyurl.com/yetu55nn

3. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015 Aug 15;5(9):2892-911. PMID: 26609494; PMCID: PMC4633915.

4. Zhou Q, Zhao H, Lu S, et al. Consensus on the lung cancer management after third-generation EGFR-TKI resistance. Lancet Reg Health West Pac. 2024 Dec 11;53:101260. doi: 10.1016/j.lanwpc.2024.101260.

5. Fang W, Zhao Y, Luo Y, et al. Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial. JAMA. 2026 Jun 17:e267745. doi: 10.1001/jama.2026.7745.