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

Akeso and Summit Therapeutics' PD-1/VEGF inhibitor ivonescimab has demonstrated significant efficacy in delaying tumor progression in patients with advanced 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, enrolled over 530 patients with squamous NSCLC who had not received prior systemic therapies. Results showed that ivonescimab in combination with chemotherapy reduced the risk of progression or death by 40% compared to BeOne Medicines' Tevimbra plus chemotherapy.

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. The objective response rate was also higher in the ivonescimab group at 75.9%, versus 66.5% for Tevimbra.

Dave Gancarz, chief business & strategy officer at Summit, emphasized the drug's performance across PD-L1 expression levels. "Ivonescimab showed a PFS advantage of 45% in patients with PD-L1 expression below 1%, 36% in those with scores between 1% to 49%, and 29% in patients with PD-L1 scores of at least 50%," he stated.

Safety Profile and Regulatory Outlook

While grade 3 or above treatment-related adverse events were more frequent in the ivonescimab group (63.9% vs 54.3%), the rate of treatment discontinuation remained low at 3.4% for ivonescimab and 4.2% for Tevimbra.

Chinese authorities are currently reviewing Akeso's application for the HARMONi-6 regimen in first-line squamous NSCLC. However, the absence of overall survival (OS) data in the ESMO presentation has raised questions about the drug's potential in the U.S. market, where the FDA typically requires statistically significant OS benefits for approval.

Global Development and Future Prospects

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 treatment. This study includes both squamous and nonsquamous histologies and involves 1,080 patients.

The pharmaceutical industry is closely watching 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 Gancarz noted, "Ivonescimab's bispecific construct allows it to reach patients who historically have not been able to receive PD-1/L1 inhibitors and VEGF medicines as separate drugs."

As Akeso and Summit continue to develop ivonescimab, the drug's performance in global trials and its ability to demonstrate significant overall survival benefits will be crucial in determining its future in the competitive landscape of NSCLC treatment.