Ivonescimab Slashes Death Risk by 34% in Advanced Squamous Lung Cancer at ASCO 2026

Ivonescimab Slashes Death Risk by 34% in Advanced Squamous Lung Cancer at ASCO 2026

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Akeso’s first-in-class PD-1xVEGF bispecific antibody ivonescimab (AK112) took center stage. Interim results from the Phase 3 HARMONi-6 (AK112-306) trial showed that combining ivonescimab with chemotherapy slashed the risk of death by 34% compared to a standard PD-1 inhibitor plus chemotherapy combination in patients with previously untreated, advanced squamous non-small cell lung cancer (NSCLC). This is the first time a China-only dataset was selected for presentation at ASCO’s prestigious plenary session.

Clinical Efficacy and Survival Benefits

The trial randomized 532 patients in China to receive either ivonescimab plus chemotherapy or the anti-PD-1 drug tislelizumab (Tevimbra) plus chemotherapy.

• Overall Survival (OS): Ivonescimab plus chemotherapy improved median OS by 4.2 months, reaching 27.9 months compared to 23.7 months in the control arm (Hazard Ratio = 0.66, p-value = 0.0017, meeting the prespecified statistical significance boundary of 0.0049).
• Subgroup Performance: The survival benefit was consistent across PD-L1 expression levels, returning a 36% death-risk reduction in PD-L1-negative patients and a 32% reduction in PD-L1-positive patients.

Historically, separate vascular endothelial growth factor (VEGF) inhibitors (such as bevacizumab) have been contraindicated in squamous NSCLC due to life-threatening risks of pulmonary hemorrhage. The bispecific approach bypassed this constraint, with Grade 3 or higher hemorrhages occurring in only 2.6% of patients in the ivonescimab arm, compared to 0.8% in the control arm.¹

"With a statistically significant 34% improvement on overall survival (OS), ivonescimab plus chemotherapy became the first regimen to beat the established standard of a PD-1 inhibitor plus chemo in patients with previously untreated, advanced squamous non-small cell lung cancer.²" — Angus Liu, Fierce Pharma

Notable Caveats and Global Applicability

Despite the historic plenary presentation and robust overall survival data, experts urged caution regarding whether the findings can immediately change clinical practice globally:

• Short Follow-Up: The median follow-up of 21.4 months is shorter than the median overall survival of either arm, leaving the long-term survival curves somewhat immature.
• Age Discrepancies: The trial uniquely excluded patients over 75 years of age. Crucially, in patients aged 65 and older, ivonescimab plus chemotherapy demonstrated no survival benefit over the control arm (with a hazard ratio near 1.0). This mirrors historical trials where older patients suffered higher toxicities from VEGF-targeted therapies.
• Patient Demographics: The study was conducted almost exclusively in men in China, whereas typical global squamous cell trials enroll at least 20% women.

ASCO discussant Dr. Julie Brahmer, director of the thoracic oncology program at Johns Hopkins, described the results as "provocative" rather than practice-changing for the global population, stating:

"Right now, I would say no, it’s not applicable to the global patient population... We really do need that next wave of Harmoni studies." — Dr. Julie Brahmer, Johns Hopkins (quoted in Fierce Pharma)

The global applicability of ivonescimab will depend on ongoing and future international trials—specifically the HARMONi-3 and HARMONi-7 studies—which are enrolling more diverse global populations.