Three years after the first patient enrolled in HARMONi-2, ivonescimab has done something pembrolizumab monotherapy has not been beaten at in a randomized Phase III head-to-head trial for first-line PD-L1-positive NSCLC: it extended median overall survival by more than eight months. At the 2026 World Conference on Lung Cancer, Akeso reported that ivonescimab hit 30.8 months median OS versus 22.6 months for pembrolizumab (HR 0.73; 95% CI 0.57–0.95; P=0.009), a 27% reduction in the risk of death across 398 patients followed for a median of 36 months.
The survival gap widened over time. At two years, 57.9% of ivonescimab patients were alive versus 48.0% on pembrolizumab; at three years, 45.0% versus 33.1%. The PD-L1-high subgroup (TPS ≥50%) was the standout: median OS with ivonescimab was not yet reached, against 23.2 months for pembrolizumab (HR 0.58). That is the population where pembrolizumab earned its original FDA approval in 2016 and where it has been hardest to displace. The squamous subgroup also showed a substantial difference, 30.5 versus 19.3 months (HR 0.65), and that matters because roughly 45% of HARMONi-2 patients had squamous disease. A large share of those had central tumors or cavitation, features that have traditionally made oncologists cautious with anti-VEGF agents; Akeso reports no apparent increase in bleeding risk in that group, though the trial was not powered to formally test that question.
The OS data follow a May 2024 interim analysis that confirmed the primary PFS endpoint: 11.14 months with ivonescimab versus 5.82 months with pembrolizumab (HR 0.51, P<0.0001). That result supported Chinese regulatory approval in 2025, though that approval covered a different indication, EGFR-mutated non-squamous NSCLC after TKI failure. The PD-L1-positive first-line setting resolved in HARMONi-2 is the global commercial prize, and Akeso is now running HARMONi-7, an international multicenter Phase III trial of ivonescimab monotherapy versus pembrolizumab in PD-L1-high patients specifically, which will be the dataset regulators outside China will require.
Ivonescimab combines PD-1 blockade with VEGF inhibition in a single bispecific antibody, a mechanism tested in combination form by IMpower150 but not previously beaten head-to-head as monotherapy at the OS level. The number to watch now is HARMONi-7 enrollment pace: that trial’s readout will determine whether a Western regulatory filing is years away or approaching.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
