First-line treatment for patients with advanced squamous non–small cell lung cancer (NSCLC) typically involves chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors, but there remains a need to improve survival outcomes, especially for patients with low programmed death-ligand 1 (PD-L1) expression. The phase 3 HARMONi 6 trial explored whether a dual-targeted approach combining PD-1 inhibition and VEGF blockade can improve the clinical outcomes beyond the current standard of care.
A total of 532 previously untreated patients with stage III to IV squamous NSCLC received either ivonescimab, a dual-targeted anti–PD-1 and anti-VEGF immunotherapy or tislelizumab, a PD-1 inhibitor, each in combination with carboplatin and paclitaxel, followed by maintenance monotherapy.
At a median follow-up of 21.4 months, ivonescimab plus chemotherapy was associated with improved overall survival (OS) compared with the PD-1–based regimen. Median OS was 27.9 months versus 23.7 months (hazard ratio, 0.66), reflecting a 34% reduction in the risk of death. The survival advantage was consistent across PD-L1 subgroups, including patients with PD-L1 <1%, where median OS had not yet been reached with ivonescimab, compared with 18.6 months in the control arm.
These results may be particularly relevant for patients with low PD-L1 expression, a population that has historically derived less benefit from PD-1 inhibition alone. Because the study was conducted in China, additional studies are ongoing to evaluate the generalizability of these findings in broader global populations.
The safety profile was generally consistent with prior experience for dual PD-1/VEGF blockade. Rates of bleeding events were slightly higher with ivonescimab than with the comparator regimen, but no unexpected safety signals were identified.
These findings support dual PD-1 and VEGF blockade as a promising first-line treatment strategy for advanced squamous NSCLC and may be particularly relevant for patients with low PD-L1 expression.
Source: Chen Z, Yang F, Luo Y, et al. HARMONi 6: phase 3 trial of ivonescimab plus chemotherapy vs tislelizumab plus chemotherapy in previously untreated advanced squamous NSCLC—overall survival results. Presented at: ASCO Annual Meeting. May 29-June 2, 2026; Chicago, IL. Abstract LBA4.