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

Area of Science:

• Oncology
• Immunology
• Diagnostics

Background:

• Cancer immunotherapies like atezolizumab offer significant benefits for non-small cell lung cancer (NSCLC) and urothelial cancer (UC).
• Accurate identification of patients who will respond to atezolizumab is crucial for optimizing treatment outcomes.
• Programmed-death ligand 1 (PD-L1) expression is a key biomarker for predicting response to anti-PD-L1 therapies.

Purpose of the Study:

• To describe the performance and analytical validation of the VENTANA PD-L1 (SP142) Assay.
• To evaluate the assay's ability to measure PD-L1 expression on both tumor cells (TC) and tumor-infiltrating immune cells (IC) in NSCLC and UC tissues.
• To assess the reliability and reproducibility of PD-L1 assessment using the VENTANA PD-L1 (SP142) Assay.

Main Methods:

• Immunohistochemistry (IHC) was used to measure PD-L1 expression.
• The VENTANA PD-L1 (SP142) Assay was analytically validated for specificity, sensitivity, and staining capabilities on TC and IC.
• Reader precision, reproducibility, and pathologist training effectiveness were evaluated.

Main Results:

• The VENTANA PD-L1 (SP142) Assay demonstrated robust performance in evaluating PD-L1 expression on both TC and IC across various clinical cut-offs in NSCLC and UC.
• Reader precision showed high overall agreement with consensus scores.
• Pathologists achieved high accuracy (≥95.0% agreement) after training, meeting predefined criteria.

Conclusions:

• The VENTANA PD-L1 (SP142) Assay is a precise and reliable diagnostic tool for assessing PD-L1 expression in NSCLC and UC.
• The assay can aid in identifying patients who may benefit most from atezolizumab immunotherapy.
• The assay's ability to evaluate PD-L1 on both tumor and immune cells enhances its utility in personalized cancer treatment strategies.