TEST:

PD-L1 IHC 28-8 pharmDx

"Agilent Technologies Inc...announced its PD-L1 IHC 28-8 pharmDx kit has received two new companion diagnostic indications approvals under EU IVDR1, expanding the eligibility of treatment to early-stage non-small cell lung cancer (NSCLC) and previously untreated advanced melanoma patients....PD-L1 IHC 28-8 pharmDx is approved for exclusive use with the Agilent Autostainer Link 48 advanced staining solution....When used in conjunction with the PD-L1 IHC 28-8 pharmDx as a companion test, in the European Union: (a) resectable NSCLC patients with PD-L1 expression ≥1% and at high risk of recurrence may be eligible for treatment with Bristol Myers Squibb’s OPDIVO (nivolumab) in combination with platinum based chemotherapy; and (b) patients 12 years of age and older with tumor cell PD-L1 expression < 1% that have previously untreated advanced (metastatic or unresectable) melanoma may be eligible for treatment with Bristol Myers Squibb’s Opdualag (nivolumab and relatlimab)."

ICIs significantly improve survival outcomes in patients with recurrent pulmonary pleomorphic carcinoma, particularly in those with high PD-L1 expression. Early postoperative recurrence and rapid progression have been observed, making therapeutic intervention challenging. Close follow-up is crucial, and ICIs become a pivotal treatment option for managing this highly aggressive cancer.

In this controlled experiment the PD-L1 assays 28-8 and SP263 concordance was high. The scoring algorithms for GEJ, GC, and EAC samples were observed as highly correlated; minor differences were likely driven by the distinct PD-L1 monoclonal antibody clones utilized in the IHC assays. These data suggest that the 2 assays are comparable for evaluating PD-L1 expression at the TAP ≥ 5% and CPS ≥ 5 cutoffs.

"Agilent’s PD-L1 IHC 28-8 pharmDx (Code SK005) provides clinically relevant information about PD-L1 expression – a critical biomarker for potential response to therapies containing anti-PD-1 antibodies such as OPDIVO (nivolumab) which has demonstrated therapeutic value across growing list of cancer types and Opdualag (nivolumab and relatimab)....PD-L1 IHC 28-8 pharmDx (Code SK005) has received European IVDR certification for nine cancer indications, including five companion diagnostic indications; non-small cell lung cancer (NSCLC), muscle invasive urothelial carcinoma (MIUC), melanoma, esophageal squamous cell carcinoma (ESCC), and gastric, gastroesophageal junction (GEJ) and esophageal adenocarcinoma."

Sponsored by ono

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

PD-L1 expression was significantly correlated with tumour location using the 22C3 pharmDx assay (CPS, p=0.014; TPS, p=0.033). Notable concordance was found among PD-L1 assays, suggesting their potential interchangeability in HNmSCC.

P1/2 | "Updated data indicate that the combination of TST001 plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer is safe and well tolerated with very encouraging anti-tumor activities, especially for patients with high/medium CLDN18.2 expression when cross comparing to historical data."

"High TLS gene expression signatures, particularly in the highest quartile, are associated with favorable outcomes in patients with high TMB or MSI-High status treated with pembrolizumab. These findings suggest that TLS status could serve as a potent biomarker to stratify patients more likely to benefit from ICI therapy, advocating for its integration into routine clinical assessments prior to ICI treatment in these specific group of patients."

The IIP was significantly predictive for a PFS benefit of Niv+Chemo over Chemo, more prominently in pts with a non-SRC histology.

High TLS gene expression signatures, particularly in the highest quartile, are associated with favorable outcomes in patients with high TMB or MSI-High status treated with pembrolizumab. These findings suggest that TLS status could serve as a potent biomarker to stratify patients more likely to benefit from ICI therapy, advocating for its integration into routine clinical assessments prior to ICI treatment in these specific group of patients.

In 451 patients, PD-L1 was determined in 223 primary tumors (pT), 62 skin/subcutaneous metastases (skin/SC), and 166 lymph node metastases (LN). A BRAF mutation (BRAFmut) was found in 186 patients (41.2%). 362 patients received ICI (80.3%) and 89 received TT (19.7%).

"Considering TC κ ≥ 1%, TC κ ≥ 50%, IC κ ≥ 1%, and IC κ ≥ 10%, the PD-L1 positivity rate was TC = 4.2-36.1% and IC = 9.7-48.6%; the overall agreement between antibodies ranged from 69.4 to 93.1%, showing fair or better agreement (κ ≥ 0.21). In CUP, PD-L1 positivity varied depending on antibodies and scoring systems, with no difference observed according to histologic or clinical subtypes."

This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.

"The 73-10 clone assay's sensitivity ranged from 78.3% to 100% (TPS ≥1%), 100% (TPS ≥50%), and 77.4% to 93.5% (IPS ≥1%), while its specificity was 97.9% to 100% (TPS ≥1%), 99.5% to 99.8% (TPS ≥50%), and 97.9% to 100% (IPS ≥1%). This exploratory evaluation of LBS 73-10 monoclonal antibody on a large set of breast, colorectal, and hepatocellular carcinomas showed the assay's technical performance is comparable to the FDA-approved companion/complementary diagnostics PD-L1 detection assays."

"In HCC, clone 28-8 seems to be more sensitive to identify gastric-type HCC. These carcinomas might be candidates for immunotherapy."

P1/2 | "Preliminary data indicate that the combination of TST001 6mg/kg Q3W plus nivolumab and CAPOX for the 1st line treatment of patients with G/GEJ cancer is safe and well tolerated with encouraging preliminary anti-tumor activities. Updated clinical data, including PFS and DoR will be reported at the time of the conference. Clinical trial information: NCT04495296."

This study provides population level data in a Canadian context on patients with gastric and GEJ adenocarcinoma with respect to HER-2 overexpression and PD-L1 status. This data will be helpful in planning allocation of clinical and financial resources as a new standard of care for these patients is established.

An AI model for the assessment of PD-L1 expression in GC using CPS was applied successfully without human intervention. The correlation in continuous CPS scores as well as the concordance in clinical categories with all pathologists was higher for the AI model than for individual pathologists on average, while at the same time, the AI model found more positive patients. This shows that by using AI more positive patients eligible for PD-L1 targeted treatment might be identified while simultaneously ensuring a level of concordance that is non-inferior to pathologists.

This GC study highlights analytical concordance in PD-L1 testing among three major PD-L1 assays when TAP and CPS scoring algorithms are prospectively applied. Independently, DIA further supports the comparability of the technical performance of the assays. These observations support flexibility in cross-application of the different PD-L1 assays and scoring algorithms currently used to characterize PD-L1–positive GC samples.

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.

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.

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.

"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.

No abstracts available

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.