• Magdalena Zajac, Anne-Marie Boothman, Yong Ben, Ashok Gupta, Xiaoping Jin, Amita Mistry, Constantine Sabalos, Alma Nielsen, Guadalupe Manriquez, Craig Barker, Joyce Antal, Peiyi Wang, Pallavi Patil, Nicole Schechter, Marlon C Rebelatto, and Jill Walker.
• From Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (Drs Zajac, Boothman, and Walker and Mr Barker); Global Medicines Development, AstraZeneca, Gaithersburg, Maryland (Dr Ben); Clinical Development (Dr Gupta and Ms Antal), Biostatistics (Dr Jin), and Translational Sciences and Pathology (Dr Rebelatto), MedImmune, Gaithersburg, Maryland; and Roche Tissue Diagnostics, Ventana Medical Systems Inc, Tucson, Arizona (Drs Mistry, Manriquez, and Patil, Mr Sabalos, and Mss Nielsen, Wang, and Schechter). Dr Ben is currently affiliated with BioAtla, San Diego, California. Dr Jin is currently affiliated with Akeso Biopharma Inc, Zhongshan, Guangdong, China. Ms Antal is currently affiliated with G1 Therapeutics Inc, Research Triangle Park, North Carolina.
• Arch. Pathol. Lab. Med. 2019 Jun 1; 143 (6): 722-731.

Context.—Clinical responses to anti-programmed death receptor-1 and anti-programmed death ligand-1 (PD-L1) agents are generally improved in patients with high PD-L1 expression compared with those with low/negative expression across several tumor types, including urothelial carcinoma.Objective.—To validate a PD-L1 immunohistochemical diagnostic test in urothelial carcinoma patients treated with the anti-PD-L1 monoclonal antibody durvalumab.Design.—The Ventana PD-L1 (SP263) assay was validated for intended use in urothelial carcinoma formalin-fixed, paraffin-embedded samples in studies addressing sensitivity, specificity, robustness, and precision, and implemented in study CD-ON-MEDI4736-1108 (NCT01693562). Efficacy was analyzed in patients classified according to prespecified PD-L1 expression cutoffs: PD-L1 high (if >1% of the tumor area contained tumor-associated immune cells, ≥25% of tumor cells or ≥25% of immune cells stained for PD-L1; if ≤1% of the tumor area contained immune cells, ≥25% of tumor cells or 100% of immune cells stained for PD-L1) and PD-L1 low/negative (did not meet criteria for PD-L1 high).Results.—The assay met all predefined acceptance criteria for sensitivity, specificity, and precision. Interreader and intrareader precision overall agreement were 93.0% and 92.4%, respectively. For intraday reproducibility and interday precision, overall agreement was 99.2% and 100%, respectively. Interlaboratory overall agreement was 92.6%. In study CD-ON-MEDI4736-1108, durvalumab demonstrated clinical activity and durable responses in both PD-L1-high and PD-L1-low/negative subgroups, although objective response rates tended to be higher in the PD-L1-high subgroup than in the PD-L1-low/negative subgroup.Conclusions.—Determination of PD-L1 expression in urothelial carcinoma patients using the Ventana PD-L1 (SP263) assay was precise, highly reproducible, and clinically relevant.

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