Akeso's Ivonescimab Plus Chemotherapy Significantly Improves Overall Survival in EGFR-Mutant NSCLC: Final HARMONi-A Phase III Results Published in JAMA

For patients with EGFR-mutant lung cancer whose tumors have progressed on targeted therapy, the treatment options have long been bleak. Immunotherapy combinations that work wonders in other lung cancers have consistently failed this population—until now.

On June 18, 2026, Akeso announced that the final overall survival analysis of the Phase III HARMONi-A trial has been published in JAMA, the Journal of the American Medical Association. The results show that ivonescimab, a first-in-class PD-1/VEGF bispecific antibody, combined with chemotherapy significantly extended survival in patients with EGFR-mutant non-squamous non-small cell lung cancer whose disease progressed on EGFR-TKI therapy.

A Dual Victory

With a median follow-up of 32.5 months, ivonescimab plus chemotherapy reduced the risk of death by 26% compared to chemotherapy alone (hazard ratio 0.74, P=0.02). Median overall survival reached 16.8 months in the treatment arm versus 14.1 months in the control arm.

The benefit held across key subgroups. Patients with brain metastases saw a hazard ratio of 0.61. Those with EGFR 19Del mutations achieved an HR of 0.83, while patients with L858R mutations saw an HR of 0.60.

HARMONi-A is the first Phase III immunotherapy trial in EGFR-TKI-resistant non-squamous NSCLC to achieve statistically significant and clinically meaningful improvements in both progression-free survival and overall survival. The PFS interim analysis was previously published in JAMA in 2024 and presented as an oral report at the ASCO annual meeting.

Filling a Critical Gap

"Patients with EGFR-TKI-resistant non-squamous NSCLC have long faced a dilemma where immunotherapy offered no benefit," said Professor Zhang Li of Sun Yat-sen University Cancer Center, the study's principal investigator. "Previous PD-1 monoclonal antibody combinations with chemotherapy failed to significantly improve overall survival in this population. HARMONi-A not only achieved positive PFS results but also confirmed in the final OS analysis that ivonescimab can deliver significant survival benefit, filling a critical clinical gap."

The safety profile remained consistent with the known profile of ivonescimab. No new safety signals emerged during the extended follow-up, and the incidence of common treatment-related adverse events was similar between the two groups.

Regulatory Momentum

Based on HARMONi-A data, China's National Medical Products Administration approved ivonescimab in May 2024 for EGFR-TKI-progressed locally advanced or metastatic non-squamous NSCLC. It became the first approved bispecific antibody with dual "tumor immunotherapy plus anti-angiogenesis" mechanisms. The drug was included in China's National Reimbursement Drug List in November 2024.

A second indication followed in April 2025, after the HARMONi-2 trial demonstrated ivonescimab's superiority over pembrolizumab as first-line treatment for PD-L1-positive advanced NSCLC. In that head-to-head Phase III study, ivonescimab reduced the risk of progression or death by 49%, making it the first drug to prove superior efficacy to the global "blockbuster" pembrolizumab in a head-to-head trial. This second indication was added to the National Reimbursement Drug List in December 2025.

A Global Strategy

Akeso has built an extensive pipeline around ivonescimab, with eight registrational or Phase III trials underway in lung cancer alone. These include first-line NSCLC regimens comparing ivonescimab against pembrolizumab combinations, trials in EGFR-TKI-progressed populations, and studies targeting PD-L1 high-expression tumors.

Beyond lung cancer, the company is pursuing first-line indications in biliary tract cancer, head and neck squamous cell carcinoma, triple-negative breast cancer, colorectal cancer, and pancreatic cancer. More than 50 innovative drug candidates are in development, with 27 in clinical trials and eight already commercialized.

In December 2022, Akeso licensed partial overseas rights of ivonescimab to US-based Summit Therapeutics in a deal valued at up to $5 billion plus double-digit percentage royalties—a record for Chinese new drug licensing at the time.

The company's first bispecific antibody, cadonilimab—a PD-1/CTLA-4 dual-targeting drug—was approved in June 2022 as the world's first tumor immunotherapy bispecific antibody. Its antibody penpulimab received FDA approval for two nasopharyngeal carcinoma indications in April 2025.

For patients who once had few options after EGFR-TKI failure, the HARMONi-A results offer something new: evidence that a bispecific antibody can deliver what single-agent immunotherapies could not.