Ivonescimab Beats a PD-1 Standard in First-Line Squamous Lung Cancer at ASCO, the First China-Originated Drug to Reach the Society's Plenary
HARMONi-6 showed Akeso's PD-1/VEGF bispecific cut the risk of death by 34% versus tislelizumab plus chemotherapy, and reached the ASCO plenary for the first time for a China-originated cancer drug.
Overview
A bispecific antibody developed in China outperformed a PD-1 checkpoint inhibitor head-to-head in the first-line treatment of advanced squamous non-small cell lung cancer, a setting where survival gains have been hard to come by. According to The ASCO Post, patients in the phase 3 HARMONi-6 trial who received ivonescimab plus chemotherapy reached a median overall survival of 27.9 months, compared with 23.7 months for those treated with tislelizumab plus chemotherapy (hazard ratio = 0.66, 95% CI = 0.50–0.87, one-sided P = .0017). As reported by PR Newswire, the result “marks the first time a China-originated investigational oncology drug has been selected for the ASCO Plenary Session in the society’s 61-year history.”
What We Know
The results were featured in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and, per The ASCO Post, the multicenter study enrolled 532 patients in China with stage IIIB, IIIC, or IV squamous NSCLC who had not received prior systemic therapy. Participants were randomly assigned to receive either ivonescimab plus paclitaxel and carboplatin (n = 266) or tislelizumab plus the same chemotherapy regimen (n = 266). The trial is described in its Lancet report as an interim overall survival analysis of a randomised, double-blind, phase 3 trial in China.
Ivonescimab is, in the words of PR Newswire, a “first-in-class PD-1/VEGF bispecific antibody” — a single molecule that blocks the PD-1 immune checkpoint and the VEGF angiogenesis pathway at once. According to The ASCO Post, treatment with ivonescimab reduced the risk of death by 34% during the study period.
The trial’s primary endpoint was progression-free survival. According to CancerNetwork, median PFS was 11.1 versus 6.9 months (HR, 0.60; 95% CI, 0.46–0.78; P <0.0001). The same source reports that the 12-month overall survival rate was 78.9% in the ivonescimab arm versus 72.2% in the tislelizumab arm, and the 24-month rate was 64.7% versus 48.6%.
Per CancerNetwork, the 532 patients were randomly assigned 1:1 to receive ivonescimab (20 mg/kg every 3 weeks) plus carboplatin (AUC 5) and paclitaxel (175 mg/m²) for up to 4 cycles followed by ivonescimab maintenance for up to 24 months, or tislelizumab (200 mg every 3 weeks) plus the same chemotherapy backbone.
Benefit across PD-L1 levels
One notable feature of the data is that the survival benefit did not depend on PD-L1 expression, the biomarker that typically governs how well checkpoint inhibitors work. According to CancerNetwork, among patients with PD-L1 tumor proportion score less than 1%, the hazard ratio for overall survival was 0.64, and among those with a score of 1% or greater it was 0.68; across narrower strata, the hazard ratios were 0.67 for 1% to 49% and 0.64 for 50% or greater. By contrast, The ASCO Post notes that in the control arm outcomes were strongly influenced by PD-L1 status, with median overall survival of roughly 27 months among patients with PD-L1 expression of at least 1% versus about 19 months among those below 1%.
Safety
According to CancerNetwork, any-grade hemorrhage occurred in 24.8% of ivonescimab-treated patients versus 12.1% in the tislelizumab arm, and hypertension in 14.7% versus 5.7%. The same source reports that grade 3 or higher immune-related adverse events were observed at an equal rate of 14% in both arms.
Why It Matters
Squamous NSCLC has historically lagged behind non-squamous disease in treatment advances. The trial’s principal investigator framed the result in those terms. As quoted by The ASCO Post, Shun Lu, MD, PhD, of Shanghai Chest Hospital, Jiao Tong University School of Medicine, said: “Squamous [NSCLC] is associated with worse clinical outcomes than nonsquamous [NSCLC]. This is one of very few studies in advanced squamous [NSCLC] that has shown median survival beyond 2 years.”
The head-to-head design is also unusual. Rather than testing the new drug against chemotherapy alone, HARMONi-6 pitted ivonescimab against an active PD-1 inhibitor, tislelizumab, both on top of the same chemotherapy. According to PR Newswire, Lu also said: “HARMONi-6 is the first global Phase III study in lung cancer to show statistically significant improvements in both OS and PFS compared with PD-1 plus chemotherapy.”
What We Don’t Know
The trial enrolled exclusively in China, leaving open how the results generalize to other populations and to comparators used elsewhere. The overall survival figure reported at ASCO is an interim analysis, per the trial’s Lancet report, so the final survival estimate could shift with longer follow-up. HARMONi-6 also did not test ivonescimab against pembrolizumab-based regimens common in Western practice. Regulatory next steps for the drug in markets outside China were not detailed in the materials reviewed here.