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Background: PD-L1 IHC 22C3 pharmDx is an FDA-approved companion diagnostic to pembrolizumab across multiple tumor types designed for use on the Autostainer Link 48 (AL48). Many pathology laboratories do not have access to the AL48 and therefore do not use PD-L1 IHC 22C3 pharmDx to assess PD-L1 status. As a result, these laboratories often assess PD-L1 using laboratory-developed tests (LDTs) on the Ventana BenchMark platform. We compared our PD-L1 22C3 antibody-based LDT on the BenchMark XT platform with PD-L1 IHC 22C3 pharmDx. Data using head and neck squamous cell carcinoma (HNSCC) and urothelial carcinoma (UC) samples alone have previously been presented (Vainer GW et al. 31st European Congress of Pathology; September 7-11, 2019). In the current study, we performed a pan-tumor analysis that also included samples from patients with esophageal SCC (ESCC). Methods: The LDT used for this analysis has been described (Neuman T et al. J Thorac Oncol. 2016;11:1863-1868). Tumor specimens from patients with HNSCC, UC, and ESCC were stained with the 22C3 antibody, scored using the LDT on the BenchMark XT platform, and compared with PD-L1 IHC 22C3 pharmDx by one trained pathologist. PD-L1 was measured using the combined positive score (CPS) by the pathologist using standard cutoffs (HNSCC, ≥1; UC and ESCC, ≥10). After PD-L1 status was determined using the LDT and PD-L1 IHC 22C3 pharmDx, the agreement between both assays was measured. Results: Samples from 327 patients with HNSCC (n = 126), UC (n = 121), and ESCC (n = 80) were evaluated for this study. The pan-tumor intraclass correlation coefficient (ICC) of PD-L1 CPS as a continuous variable was 0.96 (95% CI, 0.95-0.97); Spearman correlation was 0.95. Among patients with ESCC, ICC was 0.92 (95% CI, 0.88-0.95) and Spearman correlation was 0.89. The clinical interpretation of PD-L1 status (CPS ≥10) for ESCC samples using the 22C3 antibody LDT on the BenchMark XT platform and PD-L1 IHC 22C3 pharmDx resulted in a negative percentage agreement of 92% (95% CI, 80-97), a positive percentage agreement of 88% (95% CI, 74-95), and an overall percentage agreement of 90% (95% CI, 81-95). Conclusions: The 22C3 antibody-based LDT on the BenchMark XT platform demonstrated high concordance with the FDA-approved PD-L1 IHC 22C3 pharmDx across tumor types and in patients with ESCC alone. These findings suggest the comparability of PD-L1 IHC 22C3 pharmDx with an LDT based on the 22C3 antibody across several tumor types. This analysis will be expanded to include additional indications for inclusion in the presentation. Citation Format: Gilad W. Vainer, Ghadeer Zatara, Lingkang Huang, Kenneth Emancipator, Shanthy Nuti. Analytical comparison of a PD-L1 22C3 antibody LDT protocol on the BenchMark XT and PD-L1 IHC 22C3 pharmDx: Analysis of pan-tumor and esophageal cancer samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 503.