Akeso and Summit's Ivonescimab Shows Promise in First-Line NSCLC Treatment

Akeso and Summit Therapeutics' novel PD-1/VEGF bispecific antibody, ivonescimab, has demonstrated significant efficacy in first-line treatment of non-small cell lung cancer (NSCLC), according to data presented at the 2025 European Society for Medical Oncology (ESMO) congress in Berlin.

HARMONi-6 Trial Results

The Phase III HARMONi-6 study, conducted in China, showed that ivonescimab in combination with chemotherapy reduced the risk of progression or death by 40% compared to BeOne Medicines' Tevimbra (PD-1 inhibitor) plus chemotherapy in patients with first-line squamous NSCLC. Patients receiving ivonescimab plus chemotherapy achieved a median progression-free survival (PFS) of 11.4 months, compared to 6.9 months in the Tevimbra arm.

Dave Gancarz, chief business & strategy officer at Summit, highlighted the drug's performance: "Ivonescimab's progression-free survival performance landed firmly above expectations, and on the top end of investor sentiment."

The efficacy advantage was consistent across PD-L1 expression levels:

• PD-L1 expression <1%: 45% PFS improvement
• PD-L1 expression 1-49%: 36% PFS improvement
• PD-L1 expression ≥50%: 29% PFS improvement

Safety Profile and Potential Advantages

Ivonescimab's bispecific design appears to offer a unique safety profile. While grade 3 or above treatment-related adverse events were more frequent in the ivonescimab group (63.9% vs 54.3%), discontinuation rates remained low (3.4% vs 4.2%). VEGF-related toxicities were more common in the ivonescimab arm, but rates of severe proteinuria, hemorrhage, and hypertension were generally low.

Gancarz emphasized the potential of ivonescimab to reach patients who have historically been unable to receive separate PD-1/L1 inhibitors and VEGF medicines, particularly in squamous NSCLC where VEGF inhibitors like bevacizumab are contraindicated due to the risk of pulmonary hemorrhage.

Future Outlook and Regulatory Considerations

While the HARMONi-6 data are promising, overall survival (OS) data remain immature. The absence of OS information has raised some concerns, although Gancarz attributed this to data immaturity rather than poor performance.

Chinese authorities are currently reviewing Akeso's application for the HARMONi-6 regimen in first-line squamous NSCLC. The global pharmaceutical community is now focused on Summit's ongoing HARMONi-3 trial, which is testing ivonescimab against Merck's Keytruda in combination with chemotherapy for first-line NSCLC treatment, including both squamous and nonsquamous histologies.

As the first product in the PD-(L)1xVEGF bispecific class to reach this stage, ivonescimab's performance will be closely watched for its potential to reshape the landscape of cancer immunotherapy.