Targeted antibody improves outcomes for patients with advanced lung cancer who have faced treatment resistance

UT MD Anderson Research News September 04, 2026

• Phase 3 HARMONi study evaluated ivonescimab plus chemotherapy for patients with EGFR-mutant lung cancer whose tumors stopped responding to treatment

• This combination cut the risk of cancer progression nearly in half compared to chemotherapy alone

• Patients on ivonescimab-chemotherapy treatment lived more than two months longer without their cancer worsening

HOUSTON, SEPTEMBER 4, 2026 — Patients with EGFR-mutant non-small cell lung cancer (NSCLC) who were treated with the novel bispecific immunotherapy ivonescimab plus chemotherapy were 48% less likely to experience cancer progression or death than those receiving chemotherapy alone, according to a new study from researchers at The University of Texas MD Anderson Cancer Center.

Results from the global Phase 3 HARMONi trial, published in The Lancet Oncology, revealed that patients receiving the combination lived a median of 6.8 months without their disease worsening, compared with 4.4 months for those treated with chemotherapy alone. The treatment also improved tumor responses while maintaining a manageable safety profile.

“Despite major advances in EGFR-targeted therapies, resistance remains inevitable for most patients, and treatment options after progression are limited,” said trial co-lead, Xiuning Le, M.D., Ph.D., associate professor of Thoracic/Head and Neck Medical Oncology. “These results show that adding ivonescimab to chemotherapy can extend disease control and may offer an important new option for these patients.”

How does ivonescimab address a treatment gap for patients with EGFR-mutant lung cancer? 
While patients with EGFR-mutant NSCLC experience substantial benefits from EGFR-targeted therapies, most will eventually develop resistance to those treatments. Once this occurs, platinum-based chemotherapy remains the standard treatment option despite relatively modest outcomes.

Ivonescimab is a bispecific antibody designed to target both PD-1 and VEGF, two proteins involved in tumor growth and immune evasion. Researchers believe simultaneously blocking these pathways may help overcome mechanisms of resistance in EGFR-mutant lung cancers.

What are the key findings of the HARMONi study?  
The randomized Phase 3 trial enrolled 438 patients across Asia, Europe and North America whose disease had progressed after treatment with a third-generation EGFR-targeted therapy. Patients were randomly assigned to receive either ivonescimab plus chemotherapy or chemotherapy alone. 

In addition to improving progression-free survival, ivonescimab increased tumor response rates. The combination caused tumor shrinkage in 45% of patients, compared with 34% of those receiving chemotherapy alone. Responses also lasted longer, with a median duration of 7.6 months with the combination compared to 4.2 months with chemotherapy alone.

Researchers also observed improved control of disease in the brain, a common and difficult-to-treat site of progression for these patients. Patients receiving ivonescimab had a median of 13.7 months before their cancer worsened in the brain, compared with 10.3 months for those receiving chemotherapy alone. Median overall survival was 16.8 months for patients treated with ivonescimab and 14 months for those receiving chemotherapy alone.  

The most common severe side effects were low blood cell counts and anemia. One limitation of the study was that patients in North America and Europe had less follow-up time than originally planned, meaning additional follow-up is needed to better understand the long-term survival impact of treatment.

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This study was funded by Summit Therapeutics. A full list of authors and disclosures can be found with the full paper in The Lancet Oncology.