Abstract 1235P
Background
PD-L1 IHC 28-8 pharmDx was used in conjunction with Combined Positive Score (CPS) in the phase III CheckMate -649 clinical trial sponsored by Bristol Myers Squibb to assess gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma. The assay demonstrated clinical utility in identifying patients who have the greatest overall survival benefit and progression-free survival benefit from first-line treatment with nivolumab (OPDIVO®) in combination with chemotherapy. The precision, robustness, and external reproducibility of PD-L1 IHC 28-8 pharmDx was assessed in gastric, GEJ, and esophageal carcinoma. Analytical specimens represented multiple carcinoma subtypes, including adenocarcinoma.
Methods
Antigen retrieval was conducted on PT Link and staining was performed with Autostainer Link 48 platform using PD-L1 IHC 28-8 pharmDx. PD-L1 staining was assessed using CPS. Assay performance was validated at the CPS ≥ 5 expression cutoff.
Results
PD-L1 expression was measured on 1226 unique commercially procured cases of human FFPE specimens (439 gastric, 375 GEJ, and 412 esophageal carcinoma). Combined precision was measured in a single study which included the following conditions: inter-day, inter-run, inter-instrument, inter-operator, and reagent inter-lot. Assay precision demonstrated an overall agreement of 95.6% with a corresponding two-sided 95% confidence interval of (92.7%, 98.3%). Assay robustness was measured for: PT Link Incubation Time, PT Link Incubation Temperature, Target Retrieval Solution pH, Target Retrieval Solution Reuse, and Tissue Section Thickness. Assay robustness agreements were estimated above 90% with the lower bound of two-sided 95 percent confidence intervals at 85.5% or higher. When tested at three external sites, intra- and inter-site reproducibility, and intra- and inter-observer agreements were estimated above 91% with the lower bound of two-sided 95 percent confidence intervals at 86.0% or higher.
Conclusions
PD-L1 IHC 28-8 pharmDx has shown to be precise, robust, and reproducible in detecting PD-L1 expression in FFPE human gastric, GEJ, and esophageal carcinoma specimens using the CPS scoring algorithm.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Agilent Technologies.
Funding
Bristol Myers Squibb.
Disclosure
T. Chan: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. B. Neill: Financial Interests, Institutional, Full or part-time Employment: Agilent. A. Murga: Financial Interests, Institutional, Full or part-time Employment: Agilent. K.M. Sojka: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. S. Thakrar: Financial Interests, Institutional, Stocks/Shares: Agilent. Q. Nguyen: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. C. Felten: Financial Interests, Institutional, Other, Paid Pathology Consultant: Agilent. D. Falconer: Financial Interests, Institutional, Full or part-time Employment: Agilent. T. Marquez: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. K. Wakamiya: Financial Interests, Institutional, Stocks/Shares: Agilent. S.C. Hsu: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. D. Houston: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. S. Tabuena-Frolli: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. M. Borgert: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. S. Smith: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. E. Oroudjev: Financial Interests, Institutional, Full or part-time Employment: Agilent; Financial Interests, Institutional, Stocks/Shares: Agilent. All other authors have declared no conflicts of interest.