TEST:

PD-L1 IHC 22C3 pharmDx

Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC)...We performed a comprehensive study to investigate the expression profile of PD-L1 clone 22C3 in the US patients with ESCC. Our analysis showed that PD-L1 (22C3) expression decreased in treated specimens, and a CPS of ≥25 was associated with a favorable prognosis.

P1/2, N=540, Not yet recruiting, Shanghai East Hospital; CSPC Megalith Biopharmaceutical Co., Ltd.

P1/2, N=116, Recruiting, Cantargia AB | Trial primary completion date: Aug 2026 --> Jun 2025

P1, N=24, Active, not recruiting, Imugene Limited | Trial completion date: Mar 2026 --> May 2025 | Trial primary completion date: Feb 2026 --> Nov 2024

The patient had two metachronous lung primary cancers resected in 2022 and 2024. Due to the complete surgical resection, the sensitivity of this mutation of TKIs could not be established. This unique mutation profile still remains of paramount importance to understand if the patient relapses or presents with a new tumor with the same genetic profile.

He was subsequently treated once with a combination of chemotherapy and immunotherapy, and has been followed up for 34 months. Currently, the patient continues to survive with tumor.

P1, N=18, Not yet recruiting, Emory University | Initiation date: Sep 2024 --> Dec 2024

P2, N=30, Recruiting, Dwight Owen | Suspended --> Recruiting

No abstract available

No abstract available

P2, N=44, Not yet recruiting, Instituto Nacional de Cancer, Brazil

All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis.

Ethics Approval At each site, the study was conducted in full accordance with the 21 Code of Federal Regulations, International Council for Harmonisation guidelines, institutional review board and independent ethics committee guidelines, and all other applicable local or regional regulations. All patients provided written informed consent before enrollment.View this table:View inline View popup Download powerpoint Abstract 1461 Table 1 ARC-10 study efficacy endpointsDownload figure Open in new tab Download powerpoint Abstract 1461 Figure 1 Kaplan-Meier estimate of progression-free survivalDownload figure Open in new tab Download powerpoint Abstract 1461 Figure 2 Kaplan-Meier estimate of overall survival

The subgroup with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 had the highest PFS and OS improvements with pembrolizumab alone or with chemotherapy versus chemotherapy alone. These data suggest that TMB may be predictive of the response to pembrolizumab alone or with chemotherapy in advanced urothelial carcinoma.

P2, N=100, Recruiting, Nasser Hanna | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

PD-L1 expression in ILC shows a low TC positivity rate (0-2%) with various antibody clones and a variable IC positivity rate (0-21.8%). Pleomorphic type ILC exhibits higher PD-L1 IC positivity.

P1; Recruiting --> Suspended

P2; Active, not recruiting --> Completed

Identification of multi-hit PIK3CA GA in CAPC highlights a potentially unique phenotype that may be associated with response to anti-PIK3CA targeted therapy and checkpoint inhibition, supporting relevant clinical trial designs.

P1/2; Trial primary completion date: Aug 2024 --> Aug 2026

All authors had full access to the data and vouched for the completeness and accuracy of the data and analyses, and adherence of the study to the protocol (online only). Consent All patients provided written informed consent before study entry.

Background Recent results from the KEYNOTE-811 study showed that first-line pembrolizumab was superior to placebo with respect to progression-free survival (PFS) in combination with trastuzumab and chemotherapy in patients with HER2 positive metastatic gastric cancer (GC). Conclusions The high proportion of CD4 Tregs, CD8 Tex and the elevated exhausted score in the subgroup with PD-L1 negative in HER2 positive GCs suggesting immune exclusive environment compared to HER2 and PD-L1 coexpressing group. Considering increased expression of immune checkpoint proteins other than PD-1/PD-L1, for patients with HER2-positive and PD-L1 negative, combination therapy with other immune checkpoint inhibitors rather than anti-PD-1/PD-L1 may be suggested.

Siglec-15 is a novel immunosuppressive protein expressed on tumor associated macrophages (TAMs) and tumor cells in many indications and is currently under clinical investigation (PYX-106, NCT05718557)...The co-expression of Siglec-15 and PD-L1 in tumors may inform indication selection for combination therapies. Future studies will expand this data set for NSCLC and evaluate other indications.

Background American Cancer Society estimates that 22,370 new cases of esophageal cancer were diagnosed in the United States in 2024.1 In March 2021, Pembrolizumab received FDA approval for use as monotherapy after one or more prior lines of systemic therapy for esophageal cancer patients with squamous cell histology that expresses PD-L1 (Combined Positive Score (CPS) ≥ 10) as determined by PD-L1 IHC 22C3 pharmDx...Conclusions This study demonstrates high reproducibility of PD-L1 IHC 22C3 pharmDx with respect to PD-L1 expression in esophageal cancer specimens at the CPS ≥ 1 cutoff. Ethics Approval The external reproducibility study was approved by WCG IRB, study numbers 1356915, 1357191, 1357539.

Background In the multicohort phase 2 KEYVIBE-005 study (NCT05007106), the antitumor activity of vibostolimab (anti-T-cell immunoreceptor with Ig and ITIM domains [TIGIT]) coformulated with pembrolizumab (anti–PD-1; vibostolimab/pembrolizumab) was demonstrated in patients with previously treated advanced mismatch repair–deficient (dMMR) endometrial cancer (cohort B1; n = 40; ORR, 64%) and in patients with previously untreated advanced esophageal cancer treated with vibostolimab/pembrolizumab plus 5-fluorouracil and cisplatin (cohort E; n = 40; ORR, 53%). Ethics Approval The study protocol and all amendments were approved by the institutional review board or ethics committee at each institution. Consent All patients provided written informed consent.

The study was conducted in accordance with the International Council for Harmonisation E6(R2) guidelines on good clinical practice and the principles of the Declaration of Helsinki. All patients provided written informed consent.

For patients with metastatic triple-negative breast cancer (TNBC), treatment with pembrolizumab is dependent on the accurate determination of programmed death ligand 1 (PD-L1) expression using immunohistochemistry (IHC)...In conclusion, concordance between E1L3N and 22C3 testing using CPS for PD-L1 in metastatic TNBC was >90%. However, certain cases were challenging to agree upon using current threshold criteria, highlighting the need for more standardized evidence-based methods to assess PD-L1 expression.

In conclusion, the majority of TLS were located at the invasive margin and tumor periphery, predominantly consisting of mature TLS, while IT-TLS were mainly immature. Notably, TMB was closely associated with MSI and PD-L1, indicating potential predictive value for immunotherapy in primary adenocarcinoma of jejunum and ileum.

P2; Trial completion date: Apr 2026 --> Apr 2029 | Trial primary completion date: Apr 2025 --> Apr 2026

Although our study did not establish a correlation between PBRM1 mutations and PD-L1 expression, it demonstrated that the occurrence of PBRM1-altered ccRCC with PD-L1 expression is not uncommon. Therefore, the presence of PBRM1 alterations may challenge the use of PD-L1 IHC as a predictive marker for PD-L1 blockade in ccRCC.

Samples of metastatic tumors exhibited a higher proportion of elevated PD-L1 expression, a greater number of pathway alterations, and a higher occurrence of CDKN2A copy number deletions than primary samples. This highlights the importance of reinforcing the clinical management and follow-up of patients with CDKN2A deficiency, particularly within the subset of stage I lung adenocarcinoma.

P1; Recruiting --> Active, not recruiting | N=263 --> 101 | Trial primary completion date: Aug 2025 --> May 2026

This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.

P1; Completed --> Active, not recruiting | Trial completion date: May 2022 --> Dec 2026 | Trial primary completion date: May 2022 --> Dec 2025

P2; Trial primary completion date: Aug 2024 --> Dec 2025 | Trial completion date: Feb 2027 --> Dec 2028

The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

P2, N=29, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Nov 2024 --> Nov 2025

A significant lower PD-L1 CPS in gastric carcinoma of diffuse type according to Lauren classification identified during study may contribute to revealing yet unknown PD-L1 role in microenvironmental processes of diffuse gastric carcinoma. Also, patients with high PD-L1 CPS score and high number of PD-L1 positive immune cells demonstrate significantly longer disease free and overall survival suggesting that these parameters can be applied as an additional diagnostic marker for selecting patients to undergo prophylactic and/or curative HIPEC in gastric carcinoma.

PD-L1 IHC 22C3 pharmDx demonstrates high reproducibility in staining and scoring between different testing sites. High study endpoints were achieved with OA point estimates values of 99.7% for Inter-and Intra-site evaluations using TPS ≥1% cutoff, and Inter-site (92.8%) and Intra-site reproducibility (97.0%) for TPS ≥50% cutoff. This data supports high reproducibility of the assay and is aligned with the high scores in external quality assessments, increasing confidence in clinical use of the device on NSCLC specimens.

In spite of PD-L1 overexpression, ISMC patients who treated with pembrolizumab showed no clinical responses. We confirmed that ISMC exhibits more aggressive behaviour than UEA and that all ISMCs displayed PD-L1 overexpression, which is significantly higher than that of UEA and GEA. Our data suggest that PD-L1 overexpression is associated with poor prognosis of ISMC.

In this study, the two companion diagnostic assays provided highly concordant levels of PD-L1 expression in different cancer subtypes, using the present range of clinically relevant cut-off levels. The results indicate that the 22C3 PD-L1 assay GE006 for Omnis is interchangeable for the 22C3 assay SK006 for Autostainer Link 48 and thus GE006 being applicable to be used for many cancer subtypes for PD-L1 IHC status.

We have demonstrated statistically significant associations between manually assessed results and their matched DIA-derived quantitative scores. These results validate the manual assessment process and raise the possibility of supplementing the information fed-back to participants with fully quantitative data. The lack of associative evidence for the tonsil brings into question its usefulness as a control in this setting.