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

Akeso and Summit Therapeutics' novel bispecific antibody ivonescimab has demonstrated significant efficacy in first-line non-small cell lung cancer (NSCLC) treatment, according to results presented at the 2025 European Society for Medical Oncology (ESMO) congress in Berlin. The drug, which targets both PD-1 and VEGF, showed superior progression-free survival (PFS) compared to an established PD-1 inhibitor when combined with chemotherapy.

HARMONi-6 Trial Results

In the phase 3 HARMONi-6 trial, ivonescimab plus chemotherapy reduced the risk of disease progression or death by 40% compared to BeOne Medicines' Tevimbra (a PD-1 inhibitor) plus chemotherapy in patients with first-line squamous NSCLC. The ivonescimab regimen extended median PFS by 4.2 months, reaching 11.1 months compared to 6.9 months in the control arm.

The efficacy of ivonescimab was consistent across PD-L1 expression levels:

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

Objective response rates also favored ivonescimab (75.9%) over Tevimbra (66.5%), with a longer duration of response (11.2 months vs. 8.4 months).

Safety Profile and VEGF-Related Toxicities

While grade 3 or above treatment-related adverse events were more frequent in the ivonescimab arm (63.9% vs. 54.3%), discontinuation rates remained low (3.4% vs. 4.2%). VEGF-related toxicities were more common with ivonescimab, but rates of severe events such as proteinuria, hemorrhage, and hypertension were generally low.

Dave Gancarz, chief business & strategy officer at Summit, emphasized that ivonescimab's bispecific construct allows it to be used in patients who historically could not 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.

Regulatory Outlook and Future Studies

Chinese authorities are currently reviewing Akeso's application for the HARMONi-6 regimen in first-line squamous NSCLC. While overall survival (OS) data were not presented at ESMO due to immaturity, the Chinese regulatory agency is expected to request an additional OS analysis based on previous practices.

Attention is now shifting to Summit's global HARMONi-3 trial, which is testing ivonescimab against Merck's Keytruda in combination with chemotherapy for first-line NSCLC, including both squamous and nonsquamous histologies. This 1,080-patient study aims to provide a more comprehensive evaluation of ivonescimab's potential in a broader NSCLC population.

The pharmaceutical industry is closely watching the development of ivonescimab as the first product in the PD-(L)1xVEGF bispecific class, which has the potential to become a new backbone for cancer immunotherapy. As more data emerge, ivonescimab's role in the evolving landscape of NSCLC treatment will become clearer, potentially offering a new option for patients and challenging established therapies in this critical area of oncology.