WCLC 2025 - Posters & ePosters-P1.11.65 Ivonescimab Versus Pembrolizumab for PD-L1-Positive NSCLC: A Subgroup Analysis of HARMONi-2 by Tumor PD-L1 Expression Level

P1.11.65 Ivonescimab Versus Pembrolizumab for PD-L1-Positive NSCLC: A Subgroup Analysis of HARMONi-2 by Tumor PD-L1 Expression Level

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This subgroup analysis of the phase 3 HARMONi-2 trial evaluated the efficacy and safety of ivonescimab, a novel bispecific antibody targeting PD-1 and VEGF, versus pembrolizumab as first-line monotherapy in patients with advanced PD-L1–positive non–small cell lung cancer (NSCLC) stratified by tumor PD-L1 expression levels (TPS 1-49%, 50%, and 90%). The trial enrolled 398 patients randomized 1:1 to ivonescimab (20 mg/kg IV Q3W) or pembrolizumab (200 mg IV Q3W).<br /><br />Key findings include:  <br />- Median progression-free survival (PFS) favored ivonescimab across subgroups: 8.0 vs 5.4 months (HR 0.54) in TPS 1-49%; 11.1 vs 8.2 months (HR 0.48) in TPS 50%; and median PFS was not reached in either arm in TPS 90% (HR 0.47).  <br />- Objective response rates (ORR) were higher with ivonescimab in TPS 1-49% (43% vs 31%) and TPS 50% (60% vs 48%) but comparable in TPS 90% (63% vs 64%). Disease control rates also tended to be higher with ivonescimab.  <br />- Safety profiles were manageable; serious treatment-related adverse events (TRAEs) were similar between groups in TPS 50% and 90%, but higher with ivonescimab in TPS 1-49%. Common TRAEs for ivonescimab included proteinuria, elevated liver enzymes, anemia, and lipid abnormalities, with similar rates of grade 3 hemorrhage across PD-L1 subgroups and treatment arms.<br /><br />Baseline characteristics were balanced across treatment arms and PD-L1 subgroups, including age, sex, smoking status, histology, and presence of metastases. Median follow-up was 8.7 months.<br /><br />Overall, ivonescimab demonstrated a consistent PFS benefit and favorable response rates across PD-L1 expression levels compared to pembrolizumab, with a manageable safety profile. These results support further investigation of ivonescimab monotherapy as first-line treatment for PD-L1–positive NSCLC regardless of PD-L1 TPS. Ivonescimab is not yet widely approved outside China.  <br /><br />Reference: Xiong A et al., Lancet, 2025; presented at IASLC WCLC 2025.

Asset Subtitle

Lei Wang

Meta Tag

Speaker Lei Wang

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

ivonescimab

pembrolizumab

non-small cell lung cancer

NSCLC

PD-L1 expression

tumor proportion score

progression-free survival

objective response rate

treatment-related adverse events

first-line monotherapy