Associations of Baseline Neutrophil-to-Lymphocyte Ratio with Efficacy and Toxicity of the B7H3 ADC YL201, Linked to Interleukin 6: Analysis of the Phase I/Ib Trial
Clinical Cancer Research, 2026
Hu J., Zhong X., Ma Y., Luo J., Yang T., Ma Y., Lin C., Zhang L., Zhao H., Luo F.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Purpose:
To evaluate the association between inflammation-related indicators and efficacy and toxicity of YL201, a B7H3-targeting antibody–drug conjugate (ADC).
Experimental Design:
Data in this study were derived from a large-scale, global, multicenter, phase I/Ib trial of YL201 (NCT05434234 and NCT06057922). Inflammation-related indicators, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), were calculated from peripheral blood counts at baseline and before each cycle of YL201. Cox and logistic regression analyses assessed their associations with progression-free survival (PFS), treatment response, and treatment-related adverse events (TRAE). Plasma Olink proteomics on 72 samples (54 baseline and 18 paired at efficacy evaluation) from 54 patients was used to explore proteomic changes induced by these inflammation-related indicators.
Results:
In patients receiving YL201, a high baseline NLR was associated with inferior treatment response and PFS, particularly in those with non–small cell lung cancer (NSCLC). Beyond its prognostic association, a high baseline NLR was associated with an increased risk of any-grade thrombocytopenia and a reduced risk of any-grade asthenia, nausea, and constipation. A high baseline NLR was also associated with an increased risk of grade ≥3 TRAEs. Plasma Olink proteomic analyses suggested that the interleukin (IL) 6 level might be correlated with NLR status and further influence the probability of clinical benefit.
Conclusions:
In YL201-treated patients, a high baseline NLR was associated with inferior efficacy and a distinct toxicity profile, supporting its clinical utility for patient stratification. For high-NLR patients, combination with IL6-targeted therapy might improve the efficacy and reduce the toxicity of YL201.