WCLC 2025 - Posters & ePosters-P1.11.83 Ivonescimab Versus Pembrolizumab for PD-L1-Positive NSCLC: A Subgroup Analysis of HARMONi-2 by Tumor Histology

P1.11.83 Ivonescimab Versus Pembrolizumab for PD-L1-Positive NSCLC: A Subgroup Analysis of HARMONi-2 by Tumor Histology

Pdf Summary

The HARMONi-2 phase 3 trial evaluated ivonescimab, a bispecific antibody targeting PD-1 and VEGF, versus pembrolizumab in first-line treatment of advanced PD-L1–positive non–small cell lung cancer (NSCLC), stratified by tumor histology (squamous vs non-squamous). The study enrolled 398 patients across 55 hospitals in China and assessed progression-free survival (PFS) by independent radiology review (IRRC) as the primary endpoint.<br /><br />Key findings show that ivonescimab significantly improved median PFS compared to pembrolizumab in both squamous (9.7 vs 5.8 months; HR 0.50) and non-squamous subgroups (11.1 vs 6.7 months; HR 0.55). This PFS benefit was consistent regardless of PD-L1 tumor proportion score (TPS) levels (1-49% and ≥50%). Objective response rates (ORR) were higher with ivonescimab in squamous NSCLC (53.3% vs 30.8%) and comparable in non-squamous NSCLC (47.2% vs 45.0%). Duration of response favored ivonescimab, particularly in squamous patients where median DOR was not reached versus 8.38 months with pembrolizumab. Time to response was similar or shorter for ivonescimab.<br /><br />Safety profiles were manageable with ivonescimab. In squamous NSCLC, serious treatment-related adverse events (TRAEs) were similar between groups; in non-squamous NSCLC, ivonescimab had higher TRAE rates including grade 3 events (35.5% vs 13.0%). Common TRAEs with ivonescimab included proteinuria, hypothyroidism, liver enzyme elevations, hypertension, and hypercholesterolemia. Grade 3 hemorrhage rates were low and balanced across treatments and histologies.<br /><br />Overall, the histology subgroup analysis supports ivonescimab as a promising monotherapy providing superior PFS and response rates with an acceptable safety profile compared to pembrolizumab in PD-L1–positive advanced NSCLC. These results warrant further investigation of ivonescimab in first-line treatment for both squamous and non-squamous NSCLC patients.

Asset Subtitle

Anwen Xiong

Meta Tag

Speaker Anwen Xiong

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

ivonescimab

pembrolizumab

non-small cell lung cancer

NSCLC

PD-L1 positive

progression-free survival

bispecific antibody

PD-1

VEGF

squamous vs non-squamous