TEST:

VENTANA PD-L1 (SP263) Assay

P2, N=169, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P3 --> P2 | Trial primary completion date: Aug 2024 --> May 2027

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

Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.

This preliminary study supports the use of AI algorithms for the scoring of PD-L1 and TILs in patients with NSCLC.

The phase III IMpower110 trial differed in that regard, that it clinically evaluated both the PD-L1 TC and IC score as a predictive biomarker for Atezolizumab monotherapy in patients with metastasized or locally advanced NSCLC and gained market authorization for patients with high prevalence of PD-L1 on both tumor and/or immune cells: TC3 (≥50% TC/TPS score) and/or IC3 (≥10% IC score)...Furthermore, correlations to clinical important gene alterations will be presented. This shows that for appropriate treatment decisions by the treating physician according to different marketing authorizations it is of utmost importance that every NSCLC patient should be scored not only for PD-L1 TPS/TC but also for IC.

Updated analyses from POSEIDON after median FU of >5 y showed durable long-term OS benefit with the approved regimen of T+D+CT (vs CT alone). These results support its use as a 1L treatment option for pts with mNSCLC, including harder-to-treat subgroups such as those with PD-L1 TC <1%.

The updated findings, based on greater EFS maturity and further follow-up, are expected to shed further light on the full clinical benefit of the perioperative regimen with durvalumab and longer-term safety of this regimen.

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

At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS. This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC.

When we replaced FVC (%) in the multivariable analysis with forced expiratory volume in 1 s (%), diffusing lung capacity for carbon monoxide (DLco; %), or DLco (absolute), each of the pulmonary function factors showed a significant association with iOS. Pre-immunotherapy FVC (%) predicted immunotherapy-related outcomes in NSCLC patients, regardless of initial stage at diagnosis and prior treatment modalities.

Our results indicate a high intratumoral heterogeneity evaluated with 99mTciPD-L1 SPECT/CT that does not fully correlate with FDG, these preliminary findings may help explain discrepancy in biopsy sites; Therefore, this new imaging tool could be a potential diagnostic biomarker for selection and response to immunotherapy, as well as auxiliary in biopsy sampling.

P2, N=0, Withdrawn, Nykode Therapeutics ASA | N=130 --> 0 | Recruiting --> Withdrawn

A subset of PTC showed co-expression of PD-L1 and CTLA-4. These findings suggest the need for further investigation to utilise combinational immunotherapy, including anti-PD-L1 and anti-CTLA-4.

Albeit PD-L1 scoring is challenging, it provided at least moderate interobserver agreement in our study. TPS demonstrated the highest, while IC exhibited the lowest concordance. As threshold values changed, the interobserver agreement varied.

The macroscopic form according to R. Borman, the morphological type according to the classification of WHO 5th edition, 2019, and the presence/absence of signet ring cells are statistically significant parameters, where there is a significant relationship with PD-L1 expression. Positive PD-L1 status is significantly more often detected in HBV-associated gastric carcinomas. An increase in the expression level of PD-L1 clones SP263 and SP142 are significant prognostic signs that reduce the likelihood of death in patients.

Assessing TB in surgical specimens can provide information about the response to treatments, such as immunotherapy, which have been introduced into the treatment of GC in recent years. In this study, we demonstrated the relationship between TB, PD-L1 and MSI status in GC: Low grade TB, assessed by methods H.Ueno and L.Wang, correlates with MSI-positive status, but not with PD-L1-status of GC.

In conclusion, our study validates the feasibility and accuracy of PD-L1 IHC on cytology cell blocks and direct smears for NSCLC, showing high concordance, despite occasional discrepancies likely due to intratumoural heterogeneity. These findings underscore cytology’s utility in PD-L1 assessment for NSCLC management, confirming its potential as an alternative when formalin-fixed paraffinembedded specimens are unavailable. This supports the use of cytology samples in clinical decision-making and highlights the need for specialized training in PD-L1 interpretation.

Neuroblastoma is not generally a highly immunogenic tumour. However, in the present study, we have found a good percentage of these tumours with PD-L1 expression; this expression appears to be higher in better differentiated tumours, e.g. differentiating neuroblastoma and nodular ganglioneuroblastoma. This finding may represent a new potential therapeutic target for these tumours.

Our study showed the heterogeneity in PD-L1 expression with respect to major oncogenic drivers in Turkey. KRAS, BRAF, MET mutations and ALK and ROS1 rearrangements were more frequent, while EGFR and HER2 mutations were less frequent compared with the overall PD-L1 expression levels. Molecular testing of non-small cell lung carcinomas (NSCLC) for oncogenic driver mutations has become standard in pathology practice.

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.

The number of CD68- and/or CD163-positive cells increases with increasing PT histological grade, and these cells exhibit hybrid characteristics, resembling both histiocyte and myofibroblasts.

Context: Pembrolizumab is US Food and Drug Administration (FDA)–approved for recurrent/metastatic cervical carcinomas with programmed death ligand-1 (PD-L1) combined positive score (CPS ≥ 1)... These data suggest that the Ventana SP263 assay may be a reasonable surrogate for 22C3 pharmDx in aggressive CVCs being considered for anti-PD-1 therapy, but the Ventana SP142 is unlikely to be a reliable surrogate in this setting. Larger studies are needed to prove reproducible interchangeability based on College of American Pathologists recommendations.

The prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.

Conclusions : In CPI-naïve patients, rilvegostomig showed a favourable safety profile and encouraging preliminary efficacy in those with PD-L1 TPS 1‒49% and PD-L1 TPS ≥50%. Data support 750 mg Q3W as the pivotal dose for registrational studies.

Maximum grade 3/4 AE rates were similar between arms during the overall period and occurred in 15.4% and 10.6% of patients during the adjuvant period ( Table ). Conclusions : These findings, based on 18 months additional follow-up since the primary EFS analysis, further support perioperative durvalumab as a new treatment option for patients with R-NSCLC.

Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.

PD-L1 expression may differ between preoperative biopsy and surgery. CLINICAL IMPLICATIONS: When comparing the benefit of preoperative, postoperative or perioperative immunotherapy, the timing of PD-L1 expression assessment as a biomarker test for immunotherapy requires caution.

FAP is a marker for cancer-associated fibroblasts and is linked to immunosuppression and neoangiogenesis, which makes future investigation clinically relevant. We found that progression of high-risk non-muscle-invasive bladder cancer to muscle-invasive disease is less in patients with lower fibroblast activation protein-α (FAP) expression, which is a marker for cancer-associated fibroblasts.

Introduction : Accurate PD-L1 testing for non-small cell lung cancer (NSCLC) maximizes the benefits of immunotherapy drugs like Atezolizumab and Pembrolizumab. Conclusions : In China, the SP263 PD-L1 testing is the most cost-effective option for guiding immunotherapy in both stage IIA-IIIB and stage IV NSCLC patients. Cost-Effectiveness Analysis Results

Patient demographic and clinical characteristics Patient case Patient 1 Patient 2 Patient 3 Sex Male Female Female Age at ICI initiation (years) 37 62 75 Histology Squamous cell carcinoma Lymphoepithelioma-like carcinoma Squamous cell carcinoma Staging cT4N2M1a, stage IVa pT4N3M1a, stage IVa cT4N2M1a, stage IVa ECOG performance status 0 0 1 Immunohistochemical assay DAKO 22C3 DAKO 22C3 Ventana SP263, DAKO 22C3 PD-L1 expression % 100% 55% 98% (both assays) Prior and subsequent treatments Cisplatin/gemcitabine → Cisplatin/docetaxel → Pembrolizumab Cisplatin/pemetrexed → Docetaxel → Paclitaxel → Pembrolizumab → Gemcitabine Cisplatin/gemcitabine → Pembrolizumab → Paclitaxel ICI treatment cycles 1 7 6 Clinical benefit Partial response Partial response Partial response Time to irMG onset after ICI initiation (days) 16 (Mar 25 th 2020 - Apr 10 th 2020) 253 (June 24 th 2020 - Mar 4 th 2021) 27 (May 17 th 2019 - June 13 th 2019) Diagnostic tests 1. 2021. Abbreviation: AChEI, acetylcholinesterase inhibitor; CT, computerized tomography; ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; MG, myasthenia gravis; MGFA, Myasthenia Gravis Foundation of America; MRI, magnetic resonance imaging; PD-L1, programmed death-ligand 1; RNS, repetitive nerve stimulation

Conclusions : Individuals with BRAF mutations treated with frontline ICI had improved OS and PFS compared to those treated with chemotherapy. OS benefit was particularly pronounced for never-smokers and for those with class I mutations.

We report efficacy and safety after a minimum 3-yr follow up. Adults with locally advanced, nonresectable or metastatic, HER2-negative, untreated GC/GEJC were randomized (1:1) to intravenous TIS 200 mg or PBO every 3 wks + investigator-chosen CT (oxaliplatin + capecitabine or cisplatin + 5-fluorouracil). After a minimum 3-yr follow up, TIS + CT as 1L treatment for GC/GEJC continued to demonstrate clinically meaningful improvements in OS, PFS, and DoR compared with PBO + CT, with no new safety signals. These long-term data further support TIS + CT as a new 1L treatment option for advanced HER2-negative GC/GEJC. Table: 1437P aStratified.bInvestigator evaluated.

Post-op and post-chemo ctDNA positivity was a negative prognostic factor for DFS after 5y of follow up. Regardless of ctDNA status, DFS and OS benefit with atezo vs BSC was seen in pts with stage II-IIIA PD-L1 TC ≥1% NSCLC. Chemo-mediated ctDNA– was associated with longer DFS.

P1; Trial completion date: Apr 2024 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Mar 2025

At this IA, belrestotug + dostarlimab demonstrated clinically meaningful anti-tumor activity at each dose and a manageable safety profile, supporting further evaluation in pts with previously untreated, unresectable LA/M PD-L1 high NSCLC. 1. Reck M, et al.

P3; N=1150; Not yet recruiting; Sponsor:Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.

The majority of ATC are PD-L1-positive, making them candidates for anti-PD therapy. Histopathological pattern in ATC may be indicative of PD-L1 expression status. A negative PD-L1 result on needle biopsies may not preclude PD-L1 expression in other tumour foci.

All six WTs analysed for TMB showed low mutation burden. We found CD8+ lymphocytes in all analysed WTs and identified a fraction of WT (17.8% of primary and 35.8% of metastatic) with positive PD-L1 CPS, suggesting potential response to ICIs in some patients.

P2; The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

"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."