26P - An immunohistochemical PD-L1 diagnostic assay for treatment with durvalumab in urothelial cancer patients

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Magdalena Zajac
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors M. Zajac1, A.M. Boothman1, A. Nielsen2, G. Manriques2, C. Barker1, P. Wang2, P. Patil2, N. Schechter2, M. Rebelatto3, J. Walker1
  • 1Personalized Healthcare And Biomarkers, AstraZeneca, SG8 6HB - Cambridge/GB
  • 2Companion Diagnostics, Ventana Medical Systems Inc., Tucson/US
  • 3Pathology, MedImmune, Gaithersburg/US



The FDA has granted Breakthrough Therapy designation for durvalumab, an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1), for the treatment of patients with PD-L1 High inoperable or metastatic urothelial cancer (UC). AstraZeneca (AZ) in partnership with Ventana is developing the VENTANA PD-L1 (SP263) Assay to determine tumor cell (TC) and immune cell (IC) PD-L1 expression levels in samples obtained from all UC patients enrolled in AZ studies. Here we describe a PD-L1 immunohistochemical (IHC) diagnostic (Dx) test developed for UC patients treated with durvalumab.


The IHC assay uses an anti-human PD-L1 rabbit monoclonal antibody optimized for detection of both TC and IC PD-L1 expression with the OptiView DAB IHC Detection Kit on the automated VENTANA BenchMark ULTRA platform. The assay was validated for intended use in commercial UC formalin-fixed, paraffin-embedded samples in a series of studies that addressed sensitivity, specificity, robustness, and precision.


The VENTANA PD-L1 (SP263) Assay met all the predefined acceptance criteria (APA and ANA Agreement >85%), showing analytical specificity, sensitivity and precision. It demonstrated > 97% and ≥ 85% inter-reader precision agreement for TC and IC respectively. For intra-reader, it demonstrated >96% and >87% agreement for TC and IC respectively. For intra-day, it demonstrated at least >96% agreement for TC and IC and inter-day resulted >98% and 100% agreement for TC and IC respectively. Precision study for inter-antibody lot, inter-detection kit lot and intra-platform demonstrated >97% agreement for both TC and IC. Inter laboratory testing was performed at 3 external laboratories and demonstrated an overall agreement rate of 92.3%.


These data show that determination of PD-L1 expression in TC and IC in UC by the VENTANA PD-L1 (SP263) Assay is precise and highly reproducible. The clinical utility of this diagnostic assay is being studied across durvalumab clinical trials and will be presented at upcoming medical conferences.

Clinical trial identification

Legal entity responsible for the study

AstraZeneca plc


AstraZeneca plc


M. Zajac, A.M. Boothman: Employment: AstraZeneca Corporate sponsored research: AstraZeneca. A. Nielsen, G. Manriques, P. Wang, P. Patil: Employment: Ventana. C. Barker, J. Walker: Employment: AstraZeneca Stock shareholder: AstraZeneca. N. Schechter: Employment: Ventana Medical, Roche. M. Rebelatto: Employment: AstraZeneca Stock ownership: AstraZeneca Patents/Royalties: AstraZeneca Travel/accommodation expenses: AstraZeneca.