TEST:

PD-L1 IHC 28-8 pharmDx

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2-negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment...In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

PD-L1 assays by 28-8 and 22C3 showed suboptimal concordance, while inter-observer variability was not critical in advanced gastric cancer. Discordant PD-L1 results between 28-8 and 22C3 assays may be associated with unfavorable efficacy outcomes in patients treated with nivolumab plus chemotherapy.

An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1.

P2; Not yet recruiting --> Recruiting

"Therefore, the 22C3 assay may be useful for clinical decision-making for patients with NSCLC treated with combined chemoimmunotherapy. Trial registration number: UMIN 000043958."

Circulating KIM-1 and tumor PD-L1 expression may enrich for benefit from IO therapy in adjuvant ccRCC and hence holds promise for informing risk stratification and patient inclusion in neoadjuvant or adjuvant clinical trials.

Data suggested CLDN18.2 expression levels were independent of PD-L1 status, and support the use of Transcenta 14G11 antibody for CLDN18.2 detection regardless of sample collection methods, location, and patient demographics. An anti-CLDN18.2 companion diagnostic device based on 14G11 is being developed (CLDN18.2 IHC 14G11 pharmDx, Agilent Technologies, Inc.).

The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, PD-L1, Smoothened protein and β-catenin expression with the outcome in clear cell renal cell carcinoma.

E1L3N by CyCIF was highly concordant to IHC. There is a good concordance between TPS scores measured by various PD-L1 antibodies despite differences in staining quality. Additional work is underway to compare the performance of the antibodies in diverse immune cell types and in relation to additional immune regulators to better understand variability in staining.

Our findings indicate that digital pathology has a strong potential as a reliable alternative to light microscopy for assessing PD-L1 expression.Utilizing the SP263 clone and 50% threshold in PD-L1 assessment can lead to more reliable and consistent results.

"These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting."

P2 | N=32 | Recruiting | Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P1; Phase classification: P1b --> P1 | N=232 --> 321

JCOG1013, a phase 3 randomized trial, demonstrated the addition of docetaxel to cisplatin and S-1 as first-line chemotherapy was of no benefit to patients with unresectable/recurrent GC (N=741) either for overall survival (OS) or progression-free survival (PFS)... PD-L1 TPS≥1% is significantly correlated with longer OS and PFS in patients with unresectable/recurrent GC receiving first-line chemotherapy without ICIs. PD-L1 TPS should be considered as a stratification factor in randomized clinical trials for unresectable/recurrent GC. Clinical trial information: UMIN000007652.

Several genomic and transcriptomic alterations may cause paradoxical effects among TILs, PD-L1 expression and prognosis in TNBC. Investigating and targeting these factors will advance precision immunotherapy for TNBC patients.

Greater PD-L1 expression was associated with higher pCR and RCB 0–1 rates, suggesting that pts with PD-L1+, high-risk, ER+/HER2− primary BC can achieve substantial pCR rates with the addition of NIVO to NACT. Table. Summary pCR and RCB 0–1 rates by PD-L1 SP142 and 28-8 CPS at various cutoffs.

P3; Trial completion date: Jan 2024 --> Jan 2026

"AIM-PD-L1 NSCLC was clinically validated in a diagnostic pathology laboratory. With AI assistance, identification of PD-L1–positive tumor cells led to a clinically meaningful change in PD-L1 score in 5% of cases. Walk is a shareholder in PathAI."

P1b; Trial completion date: Feb 2025 --> Jan 2026 | Trial primary completion date: Feb 2025 --> Jan 2026

Several genomic and transcriptomic alterations may cause paradoxical effects among TILs, PD-L1 expression and prognosis in TNBC. Investigating and targeting these factors will advance precision immunotherapy for TNBC patients.

Background Zolbetuximab showed efficacy for gastric cancer with Claudin (CLDN)18.2 expression...Conclusions CLDN18.2 expression was observed in 38% of resected gastric cancer samples, which was consistent with previous reports. CLDN18.2 expression was not related to prognosis and specific relationship was not observed in clinical/molecular characteristics of resected gastric cancer.

No abstracts available

Introduction: While the use of immune checkpoint inhibitor, durvalumab, following concurrent chemoradiotherapy (CCRT) is standard treatment for unresectable stage III non-small cell lung cancer (NSCLC), the survival benefit for patients with epidermal growth factor receptor (EGFR) mutant NSCLC is still unclear. In patients with EGFR mutant stage III NSCLC, gefitinib maintenance after definitive CCRT demonstrated excellent PFS and OS without any new unexpected toxicity. Therefore, further large-scale prospective randomized controlled trials are needed to validate these results.

Our analysis revealed high OPA between 73-10 and 22C3 as well as between 73-10 and 28-8. Further, our results of PPA and NPA might indicate that the results of 73-10 could be translated to those of 22C3 or those of 28-8. It was also indicated that the results of 22C3 could be translated to those of 73-10.

We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

P2; Not yet recruiting --> Recruiting | Initiation date: Feb 2023 --> Jul 2023

P3; Trial completion date: Jan 2023 --> Jan 2024

We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

This study demonstrates that the location and conformation of binding sites, recognized by antibodies employed in PD-L1 diagnostic assays differ significantly and exhibit differing degrees of robustness. These findings should reinforce the need for vigilance when performing clinical testing with different PD-L1 IHC assays, particularly in the control of cold ischemia and the selection of fixation and decalcification conditions.

P2; N=23; Recruiting; Sponsor:Kidney Cancer Research Bureau

FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.

Heterozygosity level for (gt)n locus was 40 out of 67 patients (59,7%), AI was found in 22 out of 40 (59.7%). Heterozygosity level for (ttat)m locus was 48 out of 67 patients (71,6%), AI was found in 27 out of 48 (56,2%). Five patients turned out to be homozygous for both loci.

Furthermore, IHC analysis revealed that PD-L1 was expressed in macrophages in the spleen and lymph nodes from healthy cats and mast cell tumor cells. Therefore, we indicated that the clone 28-8 antibody is a valuable tool in detecting feline PD-L1, and further analysis of tumor tissues is expected in the future.

For patients with multiple tumors, inter-tumoral heterogeneity of PD-L1 expression is common. Several actionable gene mutations were found to be more commonly occurred in PD-L1-heterogenous tumors. Physicians should carefully consider PD-L1 and genomic assessments by case in order to select appropriate patients for ICI treatments.

EV budding on phagocytic stromal cells found in the blood of mNSCLC patients appears to predict for poorer PFS and OS, which is reduced with additional of PD-L1 immunotherapies. Larger validation studies are ongoing in both mNSCLC and stage III NSCLC patients, along with analysis of PD-L1 EV staining.

E1L3N can be used as a reliable alternative antibody clone to evaluate PD-L1 expression status not only in NSCLC patients but also in other cancer types.

This study is the first dataset to compare various PD-L1 assays in ESCC. Differences in classification of patients with PD-L1 high versus low/negative using clinically relevant algorithms suggest that caution should be taken when comparing data across the trials.

The SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) phase 3 studies demonstrated clinically meaningful and statistically significant improvement in PFS and OS with the CLDN18.2-targeted antibody zolbetuximab + chemotherapy (mFOLFOX6 or CAPOX, respectively) vs placebo + chemotherapy as 1L therapy in pts with CLDN18.2+/HER2− disease... Across SPOTLIGHT and GLOW, 3576 pts had valid CLDN18 IHC results; 1399 (39.1%) had CLDN18.2+ tumors. CLDN18.2 prevalence was 43.7% (513/1175) in female pts and 36.9% (886/2401) in male pts. CLDN18.2 prevalence was 44.0% (671/1524) in pts in Europe/Middle East, 37.7% (183/485) in pts in N. America, and 36.5% (479/1314) in pts in Asia Pacific.

P1b; Trial completion date: Mar 2026 --> Feb 2025

No abstracts available

P2; Not yet recruiting --> Recruiting

Programmed death-ligand 1 (PD-L1)antibody 22C3 is the approved companion diagnostic immunohistochemistry (IHC) test for treatment with pembrolizumab and cemiplimab in multiple cancer types. Finally, quantitative assessment of fresh TMA showed significant loss of signal after a deglycosylation procedure when stained with 22C3 which was not seen when stained with E1L3N. We believe this data shows that the glycan part of the 22C3 epitope is not stable over time, and that this issue should be considered when assessing archival tissue for diagnostic or research purposes.