Programmed Death-Ligand 1 Immunohistochemistry Assay Comparison Studies in NSCLC: Characterization of the 73-10 Assay.

Abstract

INTRODUCTION:

Several programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been developed independently within clinical programs for therapeutic anti-programmed cell death protein 1 (anti-PD-1) or PD-L1 antibodies, necessitating assessment of assay comparability. We characterized the Dako PD-L1 IHC 73-10 assay used in clinical trials of avelumab (anti-PD-L1) or bintrafusp alfa (M7824; bifunctional immunotherapy) and compared it with the Dako PD-L1 IHC 22C3 pharmDx assay, an approved companion diagnostic for pembrolizumab monotherapy in patients with advanced NSCLC.

METHODS:

Formalin-fixed, paraffin-embedded NSCLC tumor samples from a commercial source and from the JAVELIN Solid Tumor phase 1 trial of avelumab (NCT01772004) were stained using the 73-10 and 22C3 IHC assays with a standard protocol.

RESULTS:

Both assays displayed expected PD-L1 staining patterns. In 148 commercial NSCLC samples, the 73-10 assay stained greater than or equal to 1%, greater than or equal to 50%, and greater than or equal to 80% of tumor cells as PD-L1+ in 64.2%, 36.5%, and 23.6% of the samples, respectively, whereas the 22C3 assay stained 20.3% of the samples as greater than or equal to 50% PD-L1+. In 83 NSCLC clinical trial samples, the 73-10 assay stained 79.5% and 31.3% of the samples as greater than or equal to 1% and greater than or equal to 80% PD-L1+, respectively, whereas the 22C3 assay stained 59.0% and 21.7% as greater than or equal to 1% and greater than or equal to 50% PD-L1+, respectively. Efficacy of avelumab was similar in the subgroups classified with the 73-10 and 22C3 assays using greater than or equal to 80% and greater than or equal to 50% PD-L1+ cutoffs, with objective response rates of 26.9% and 33.3%, respectively.

CONCLUSIONS:

The 73-10 assay demonstrated high sensitivity for PD-L1 staining, and staining was comparable between the greater than or equal to 80% cutoff of the 73-10 assay and greater than or equal to 50% cutoff of the 22C3 assay.

• Authors: Hans Juergen Grote, Zheng Feng, Michael Schlichting, Christoph Helwig, Mary Ruisi, Hulin Jin, Juergen Scheuenpflug, Claudia-Nanette Gann, Zhen Su, Martin Reck, Everett E Vokes, Keith M Kerr
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 15 Issue 8 Pg. 1306-1316 (08 2020) ISSN: 1556-1380 [Electronic] United States
• PMID: 32353599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor

Topics

• B7-H1 Antigen
• Biomarkers, Tumor
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Humans
• Immunohistochemistry
• Lung Neoplasms (drug therapy)