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 delaying tumor progression compared to an established PD-1 inhibitor in combination with chemotherapy for first-line squamous non-small cell lung cancer (NSCLC) treatment. This breakthrough, presented at the 2025 European Society for Medical Oncology (ESMO) congress in Berlin, marks a potential shift in the landscape of cancer immunotherapy.

HARMONi-6 Trial Results Showcase Ivonescimab's Efficacy

The phase 3 HARMONi-6 trial, conducted in China, revealed that ivonescimab combined with chemotherapy reduced the risk of disease progression or death by 40% compared to BeOne Medicines' Tevimbra with chemotherapy in first-line squamous NSCLC patients. The ivonescimab regimen extended progression-free survival (PFS) by a median of 4.2 months, reaching 11.1 months compared to the control arm.

Notably, ivonescimab showed consistent benefits across different PD-L1 expression levels:

• 45% PFS advantage in patients with PD-L1 expression below 1%
• 36% improvement in those with PD-L1 expression between 1% to 49%
• 29% benefit in patients with PD-L1 expression of 50% or higher

The objective response rate was also superior in the ivonescimab arm at 75.9%, compared to 66.5% in the Tevimbra arm. Among responders, the duration of response was longer with ivonescimab, lasting a median of 11.2 months versus 8.4 months for Tevimbra.

Safety Profile and Regulatory Implications

While ivonescimab demonstrated a higher incidence of grade 3 or above treatment-related adverse events (63.9% vs. 54.3% for Tevimbra), the discontinuation rates remained low at 3.4% and 4.2%, respectively. VEGF-related toxicities were more frequent in the ivonescimab arm, but rates of severe proteinuria, hemorrhage, and hypertension were generally low.

Chinese authorities are currently reviewing Akeso's application for the HARMONi-6 regimen in first-line squamous NSCLC. The lack of overall survival (OS) data in the ESMO presentation has raised some concerns, although Dave Gancarz, chief business & strategy officer at Summit, emphasized that this was due to data immaturity rather than poor results.

Future Prospects and Global Development

The success of ivonescimab in HARMONi-6 has shifted attention to Summit's global HARMONi-3 trial, which is testing the drug against Merck's Keytruda in combination with chemotherapy for first-line NSCLC, including both squamous and nonsquamous histologies. This 1,080-patient trial aims to provide a comprehensive analysis of ivonescimab's efficacy across different NSCLC subtypes.

As the first product in the PD-(L)1xVEGF bispecific class to show such promising results, ivonescimab's development is being closely watched by the oncology community. The drug's ability to potentially become a new cancer immunotherapy backbone could significantly impact treatment strategies for NSCLC and possibly other cancer types in the future.