Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab

Abstract

Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision, repeatability and intermediate precision, interlaboratory reproducibility, and the effectiveness of pathologist training on the assessment of PD-L1 staining on both TC and IC were evaluated. We detail the analytical validation of the VENTANA PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that the assay reliably evaluated staining on both TC and IC across multiple expression levels/clinical cut-offs. The reader precision showed high overall agreement when compared with consensus scores. In addition, pathologists met the predefined training criteria (≥85.0% overall percent agreement) for the assessment of PD-L1 expression in NSCLC and UC tissues with an average overall percent agreement ≥95.0%. The assay evaluates PD-L1 staining on both cell types and is robust and precise. In addition, it can help to identify those patients who may benefit the most from treatment with atezolizumab, although treatment benefit has been demonstrated in an all-comer NSCLC and UC patient population.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

“…19 Previous clinical data indicate that an improved ORR to atezolizumab amongst urothelial carcinoma patients is associated with >5% positive staining for PD-L1 (as assessed by the SP142 assay) on tumor-infiltrating immune cells. 10 , 18 Conversely, PD-L1 positivity by neoplastic or immune cells (as assessed by the 22C3 assay) reportedly fails to correlate with improved objective responses to pembrolizumab in urothelial carcinoma patients.…”

“…10 , 18 In the same setting, whole-exon DNA-seq on a subset of patients demonstrated an increased likelihood for response amongst subjects with high MuB, although a considerable overlap existed between this group and individuals with low MuB. 10 , 18 These findings led to the development of IHC-based companion diagnostics for the detection of PD-L1 expression levels in tumor biopsies, including the SP142 assay 19 from Ventana Medical Systems (Tucson, AZ, USA) and the 22C3 assay 20 from Dako Inc. (Santa Clara, CA, USA). Neither of these assays, however, is currently approved by the US FDA as a companion diagnostic for predicting responses to ICBs amongst urothelial carcinoma patients (22C3 is approved for predicting responses to pembrolizumab amongst non-small cell lung carcinoma and gastroesophageal carcinoma patients; source https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm).…”

Quantitative image analysis for CD8 score in lung small biopsies and cytology cell‐blocks

“…Scoring was done in two ways for each case: (a) using the entire whole slide image (WSI) and (b) analysing discrete representative fields of view (FOVs) for each case targeting tissue spots (TS) and minimising non‐tissue area or problematic areas (eg, section folds, pigment; Figures and ). The TS was defined as the area of viable tumour cells with their associated stroma, as used in other studies evaluating immunomarkers . For cell blocks, TS was the tissue fragments of areas with clusters of tumour cells.…”

Understanding PD-L1 Testing in Breast Cancer: A Practical Approach

“…For immune cells, however, either granular cytoplasmic or (incomplete) membranous staining suffices for a positive count ( Fig. 2) [16,19,23]. The varying scoring methods are explained in the section below.…”