Introduction
Akeso has reported new data from its phase 3 HARMONi-A study indicating that ivonescimab, when added to chemotherapy, can extend survival in patients with previously treated EGFR-mutated nonsquamous non-small cell lung cancer (NSCLC). The results, presented at the 2025 Society for Immunotherapy of Cancer annual meeting, show that the treatment significantly lowered the risk of death compared with chemotherapy alone.
Key Findings
According to the final analysis, ivonescimab plus chemotherapy reduced the risk of death by 26% in this patient population. With a data cutoff in April 2025 and a median follow-up of 32.5 months, the median overall survival was 16.8 months for patients receiving ivonescimab and chemotherapy, compared with 14.1 months for those who received chemotherapy and placebo.
A Meaningful Achievement
This outcome represents the first time a phase 3 trial in the PD-(L)1xVEGF bispecific drug class has met the primary overall survival endpoint. The finding was described as a meaningful achievement for the class by analysts from Leerink Partners led by Daina Graybosch, Ph.D.
Improved Analysis
The latest analysis improved upon interim results from December 2023, when a 20% reduction in death risk was observed at a median follow-up of 17.6 months. At that time, the median overall survival was 17.1 months for the ivonescimab group and 14.5 months for the control group.
Sustained Survival Plateau
Data indicated that around 28 months into follow-up, approximately 30% of patients treated with ivonescimab remained alive with stable outcomes, with few additional deaths reported beyond that point. Graybosch’s team noted that a sustained plateau in survival could point to an immune-related mechanism contributing to the drug’s benefit.
CEO’s Perspective
Akeso CEO Michele Xia, Ph.D., said the success of ivonescimab highlights the distinct structure of the bispecific drug. “After I saw this long-term final analysis of overall survival of ivonescimab [in HARMONi-A], it really boosted my confidence in the other non-small cell lung cancer results,” Xia said. She added that the therapy’s performance in EGFR-mutant NSCLC, a setting resistant to traditional immunotherapies, supports the potential of PD-(L)1xVEGF bispecifics to replace anti-PD-1 inhibitors.
Competitive Landscape
However, other emerging treatments have also shown strong results. Kelun-Biotech recently reported phase 3 data from its sacituzumab tirumotecan (sac-TMT) program, showing a 40% reduction in death risk for Chinese patients with the same condition, achieved without the use of chemotherapy.
Future Combinations and Global Trials
In HARMONi-A, 62.7% of patients receiving ivonescimab and 72% in the control arm went on to receive additional treatments, including targeted therapies, investigational drugs, or antibody-drug conjugates (ADCs). Xia suggested that PD-1xVEGF bispecifics and TROP2 ADCs could complement each other, rather than compete, as they target cancer through different biological pathways. She said Akeso envisions ivonescimab as “the choice of combo with all different types of ADCs to work on all different types of tumor indications.”
While the HARMONi-A results strengthen ivonescimab’s clinical profile, the global HARMONi trial conducted by Summit Therapeutics, which holds development rights in the U.S., Europe, Canada, and Japan, did not reach statistical significance for overall survival. Analysts noted that the global trial’s Western subgroup data remain immature, though the trends are consistent with those seen in China.
Summit has since modified the design of its ongoing HARMONi-3 trial, which compares ivonescimab and Keytruda in combination with chemotherapy in first-line NSCLC, to analyze nonsquamous and squamous cancers separately. Despite the mixed outcomes, Summit plans to file for regulatory approval of ivonescimab later this year.
