In this phase 3 trial for advanced squamous non-small-cell lung cancer, ivonescimab plus chemotherapy significantly improved overall survival compared to tislelizumab plus chemotherapy. The median overall survival was 27.9 months versus 23.7 months, with consistent benefit across key subgroups including patients with low PD-L1 expression. The safety profile was manageable with similar rates of treatment discontinuation and immune-related adverse events between groups, despite a higher incidence of some VEGF-related events with ivonescimab.
Study
|
Randomised, double-blind, phase 3 trial [HARMONi-6] |
| Previously untreated, unresectable stage IIIB, IIIC, or IV squamous NSCLC |
| Ivonescimab + paclitaxel + carboplatin (n=266) vs tislelizumab + paclitaxel + carboplatin (n=266), 4 cycles, then maintenance monotherapy
|
Efficacy
|
mOS: 27.9 mos vs. 23.7 mos (ivonescimab vs. tislelizumab) (HR 0.66 [0.50-0.87]) |
| 24-mo OS: 64.7% vs 48.6% |
| 12-mo OS: 78.9% vs 72.2% |
| Overall survival benefit consistent across subgroups including PD-L1 <1% (HR 0.64 [0.43-0.96])
|
Safety
|
Grade >=3 AEs: neutropenia (32% vs 26%), anemia (7% vs 5%), hypertension (4% vs 2%), renal injury or proteinuria (7% vs 0%), haemorrhage (3% vs 1%) |
| Grade >=3 immune-related adverse events: 14% vs 14% |
| Treatment discontinuation due to adverse events: 5% vs 5% |
| Death due to adverse events: 4% vs 4% |
| Possible anti-VEGF-related adverse events (any grade): 60% vs 26%, mostly grade 1-2
|
Lancet. Published online May 31 2026
http://doi.org/10.1016/S0140-6736(26)00966-9
Reviewed by Ulas D. Bayraktar, MD on Jun 17, 2026
