Abstract
BackgroundThe phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data.MethodsBox and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spearman’s rank-difference correlation, Bar graph analysis, and Receiver Operating Characteristics (ROC) were used to examine the correlation between sCD26 titer variation with YS110 administration and tumor volume change, RECIST criteria evaluation and progression free survival (PFS). Mechanism for serum sCD26 titer variation was confirmed by in vitro experimentation.ResultsSerum sCD26/DPP4 titer was reduced following YS110 administration and gradually recovered until the next infusion. Serum sCD26/DPP4 titer before the next infusion was sustained at lower levels in Stable Disease (SD) cases compared to Progressive Disease cases. ROC analysis defined the cut-off level of serum sCD26/DPP4 titer variation at day 29 pre/post for the clinical outcome of SD as tumor response or PFS. In vitro experimentation confirmed that YS110 addition reduced sCD26 production from CD26-expressing tumor and non-tumor cells.ConclusionsOur study indicates that serum sCD26/DPP4 titer variation in the early phase of YS110 treatment is a predictive biomarker for evaluating therapeutic efficacy.
Highlights
The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently
Changes in levels of serum soluble CD26 (sCD26)/dipeptidyl peptidase 4 (DPP4) titer pre/post YS110 administration, as documented by Box and Whisker plot Several crucial parameters were included in this phase I trial such as 1) tumor histology: 19 MM, 6 renal cell carcinoma (RCC) and 1 UTC; 2) YS110 dose: 0.1–6 mg/kg; 3) frequency of drug administration: once every 2 weeks (Q2W) for three doses in 18 cases, once every week (Q1W) for five doses in 8 cases
Examination of background factors between Stable Disease (SD) and Progressive Disease (PD) cases indicated that no bias was found in age, BMI, absolute value of tumor volume or serum sCD26/DPP4 titer before YS110 administration, except for gender
Summary
The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The first-in-human (FIH) phase I clinical study of YS110 for CD26-expressing solid tumors (23 MM, 9 RCC and 1 urothelial carcinoma (UTC)) was recently conducted [8], demonstrating that YS110 therapy exhibited a favorable safety profile and resulted in encouraging disease control in patients with advanced/ refractory tumors. Biomarkers in cancer management may be used for the prevention, diagnosis, and selection of therapeutic method, as well as for treatment monitoring potentially. Such markers as EGFR or ALK fusion gene (lung cancer), HER2 (breast or gastric cancer), or RAS (colon cancer) are used to select optimal therapy by identifying selected genetic alteration. No serum biomarker indicating a predictive outcome during a course of cancer treatment has been heretofore identified
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