PD-L1 Immunohistochemistry Assay Comparison Studies in Non-Small Cell Lung Cancer: Characterization of the 73-10 Assay

Abstract Introduction Several PD-L1 immunohistochemistry (IHC) assays have been developed independently within clinical programs for therapeutic anti–PD-1/PD-L1 antibodies, necessitating assessment of assay comparability. We characterize the Dako PD-L1 IHC 73-10 assay used in clinical trials of avelumab (anti–PD-L1) or bintrafusp alfa (M7824; bifunctional immunotherapy) and compare it with the Dako PD-L1 IHC 22C3 pharmDx assay, an approved companion diagnostic for pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (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 ≥1%, ≥50%, and ≥80% of tumor cells PD-L1+ in 64.2%, 36.5%, and 23.6% of samples, respectively, whereas the 22C3 assay stained 20.3% of the samples as ≥50% PD-L1+. In 83 NSCLC clinical trial samples, the 73-10 assay stained 79.5% and 31.3% of the samples as ≥1% and ≥80% PD-L1+, respectively, whereas the 22C3 assay stained 59.0% and 21.7% as ≥1% and ≥50% PD-L1+, respectively. Efficacy of avelumab was similar in the subgroups classified with the 73-10 and 22C3 assays using ≥80% and ≥50% PD-L1+ cutoffs, with objective response rates of 26.9% and 33.3%, respectively. Conclusions The 73-10 assay showed high sensitivity for PD-L1 staining, and staining was comparable between the ≥80% cutoff of the 73-10 assay and ≥50% cutoff of the 22C3 assay.