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

Akeso and Summit Therapeutics' bispecific antibody ivonescimab has demonstrated significant efficacy in first-line non-small cell lung cancer (NSCLC) treatment, according to data presented at the 2025 European Society for Medical Oncology (ESMO) congress in Berlin. The drug, which targets both PD-1 and VEGF, has shown promising results in combination with chemotherapy, potentially challenging current standard-of-care treatments.

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. Ivonescimab, when combined with chemotherapy, demonstrated a 40% reduction in the risk of disease progression or death compared to BeOne Medicines' Tevimbra (a PD-1 inhibitor) plus chemotherapy.

Key findings from the trial include:

• Median progression-free survival (PFS) of 11.4 months for ivonescimab plus chemotherapy, compared to 6.9 months for Tevimbra plus chemotherapy
• Objective response rate of 75.9% for ivonescimab, versus 66.5% for Tevimbra
• Median duration of response of 11.2 months for ivonescimab, compared to 8.4 months for Tevimbra

The PFS benefit was observed across all PD-L1 expression subgroups, with hazard ratios of 0.55, 0.64, and 0.71 for PD-L1 expression levels of <1%, 1-49%, and ≥50%, respectively.

Safety Profile and Potential Advantages

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. Deaths related to side effects occurred in 3% of ivonescimab patients, compared to 3.8% in the Tevimbra group.

Dave Gancarz, chief business & strategy officer at Summit, highlighted the potential of ivonescimab's bispecific construct to reach patients who have historically been unable to receive separate PD-1/L1 inhibitors and VEGF medicines. This is particularly relevant in squamous NSCLC, where VEGF inhibitors like bevacizumab are contraindicated due to the risk of life-threatening pulmonary hemorrhage.

Regulatory Implications and Future Directions

Chinese authorities are currently reviewing Akeso's application for the HARMONi-6 regimen in first-line squamous NSCLC. While overall survival (OS) data remain immature, analysts from Truist Securities expressed confidence that final OS results are likely to be statistically significant as data mature.

The success of ivonescimab in this trial marks the first time a regimen has outperformed the combination of a PD-1 inhibitor and chemotherapy in first-line NSCLC, albeit in a China-only study. The drug's performance has met or exceeded investor expectations, with analysts from Leerink Partners and Jefferies noting that the 40% PFS improvement aligns with anticipated results.

As the first product in the PD-(L)1xVEGF bispecific class to reach this stage, ivonescimab's development is being closely watched by the industry. 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, including both squamous and nonsquamous histologies.