Abstract 5122: Identification of PD-L1 expression on circulating tumor cells as a prognostic indicator in prospective clinical trial, OMNIVORE
Authors: Bade Rory M. , Schehr Jennifer L. , Mannino Matthew C. , Bootsma Matthew L. , Emamekhoo Hamid , Zhao Shuang G. , Choueiri Toni K. , Signoretti Sabina , McKay Rana R. , Lang Joshua M. 
Published: June 2022

Abstract
Despite recent therapeutic advances for patients with renal cell carcinoma (RCC) with immunotherapies, alone or in combination with VEGF tyrosine kinase inhibitors, there are no available biomarkers to predict patient benefit or evaluate mechanisms of resistance. The known heterogeneity of RCC may explain the limited utility of biomarker testing on single-site biopsies. This has led to great interest in liquid biopsy as an accessible source of tumor cells to evaluate mechanisms of response and resistance. Given the growing use of immunotherapy (IO) in patients with RCC, and the promise of their companion diagnostics in other disease settings, we evaluated the ability of liquid biopsy quantification of PD-L1 to predict patient response to IO in the OMNIVORE clinical trial, NCT03203473. Patients on trial were given nivolumab monotherapy, followed by radiographic scans at C3D1, with follow-up scans confirming CR/PR defined as “response.” Responding patients were placed on observation, while non-responders were transitioned to the dual therapy with nivolumab and ipilimumab arm. PD-L1 and HLA I expression was quantified on circulating tumor cells (CTCs) using Exclusion-Based Sample Preparation (ESP). Single-cell protein analysis of PD-L1 and HLA I on CTCs facilitated the generation of summary statistics including average expression of all CTCs, number of CTCs categorized as PD-L1 or HLA I positive, and frequency of CTCs with either positive or negative expression. ROC curves were used to compare diagnostic sensitivity and specificity of different CTC summary statistics for 30 patients with evaluable matched baseline and arm assignment data. Kaplan-Meier curve evaluation was performed on the summary statistic identified as that with the greatest clinical value. ROC curve analysis identified the metric “number of PD-L1+ CTCs” at arm assignment as having the greatest clinical value (AUC 0.8) compared to all other CTC summary statistics evaluated, with a diagnostic sensitivity/specificity of 88/60% at a cutoff of 2.5 PD-L1+ CTCs/7.5 mL. Survival analysis showed that patients with fewer PD-L1+ CTCs had a longer durable response (68 weeks vs. 16 weeks, HR 2.9) to single agent nivolumab. These results suggest that the number of PD-L1+ CTCs is a potential biomarker of treatment response that may have utility for treatment stratification and investigation of novel combination strategies for patients with poor prognostic features. This biomarker is now being tested in multiple prospective clinical trials to further study clinical utility.
Citation Format: Rory M. Bade, Jennifer L. Schehr, Matthew C. Mannino, Matthew L. Bootsma, Hamid Emamekhoo, Shuang G. Zhao, Toni K. Choueiri, Sabina Signoretti, Rana R. McKay, Joshua M. Lang. Identification of PD-L1 expression on circulating tumor cells as a prognostic indicator in prospective clinical trial, OMNIVORE [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5122.