TEST:

VENTANA PD-L1 (SP142) Assay

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

P2, N=416, Completed, Palleos Healthcare GmbH | Active, not recruiting --> Completed

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.

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.

The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.

ACP1-High tumors exhibit a distinct molecular profile and cold TME, highlighting ACP1's potential role in PC pathogenesis and novel therapeutic targeting.

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.

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.

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.

The digital cell counts demonstrated how immune markers are coexpressed in the TIME when considering TNBC molecular subtypes and DNA repair deficiency, and how combination of immune status with DNA repair deficiency status can improve the prognostic stratification in chemotherapy treated patients. These results underscore the value and potential of integrating TIME and specific tumour intrinsic alterations/phenotypes for the molecular understanding of TNBC.

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.

The incorporation of pre-treatment TILs and PD-L1 expression status as valuable tools for optimizing patient selection for immunotherapy and managing the risks associated with chemotherapy in Chinese TNBC patients.

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.

In primary SCCs, the expression of PD-L1, PD-1, and CD8 are not associated with high-risk clinicopathological factors. We suggest that these immunohistochemical markers are more significant in advanced cases and metastatic tissues.

P3; Trial primary completion date: Jan 2024 --> Dec 2024

SCL5A2-H across all investigated tumors was associated with increased immune infiltrate and a T cell-inflamed phenotype in addition to improved survival in multiple cancer types. Future research on SGLT2 should delineate its role in cancer formation versus its association as a potential positive prognostic marker.

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.

Characteristic Overall Training Set Testing Set N 348 279 69 sex (%) female 165 (47.69) 125 (45.13) 40 (57.97) male 181 (52.31) 152 (54.87 29 (42.03) age (%) old 188 (54.34) 158 (57.04) 30 (43.48) young 158 (45.66) 119 (42.96) 39 (56.52) Smoking (%) no 220 (86.96) 174 (86.57) 46 (88.46) yes 33 (13.04) 27 (13.43) 6 (11.54) Stage (%) I 71 (20.52) 48 (17.33) 23 (33.33) II 95 (27.46) 80 (28.88) 15 (21.74) III 168 (48.55) 139 (50.18) 29 (42.03) IV 12 (3.47) 10 (3.61) 2 (2.90) PD-L1_score (%) ≥ 50% 45 (12.93) 37 (13.26) 8 (11.59) < 1% 156 (44.83) 125 (44.80) 31 (44.93) 1-49% 147 (42.24) 117 (41.94) 30 (43.48) PD-L1_clone (%) 22C3 330 (94.83) 264 (94.62) 66 (95.65) SP142 17 (4.89) 14 (5.02) 3 (4.35) ZR3 1 (0.29) 1 (0.36) 0 (0.00) Pathology (%) LUAD 288 (83.48) 231 (83.70) 57 (82.61) LELC 9 (2.61) 4 (1.45) 5 (7.25) other 12 (3.48) 9 (3.26) 3 (4.35) LUSC 36 (10.43) 32 (11.59) 4 (5.80) Figure 1. Model Evaluation of Testing Set (A) and ROC of Two Sets (B).

Overall, our findings suggest that a subset of MBC and GCS cases may benefit from immune checkpoint inhibitor therapy. Our findings also illustrate unique aspects of PD-L1 expression patterns in these tumors which may harbor additional prognostic and therapeutic significance.

This is the largest combined clinicogenomic analysis of FOLH1 expression in PC. Tumors with high FOLH1 are molecularly and immunologically distinct, providing insights for distinct therapeutic strategies in this group.

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.

We conclude that certain parameters of poor prognosis such as high histologic grade of the tumour, presence of lymphovascular invasion, clinically positive axillary lymph nodes and high IC count correlate with PD-L1 expression in HER2-positive BC, but we did not find the potential of PD-L1 to predict response to anti-HER2 neoadjuvant treatment.

The patient was treated with Pembro+Gem+CBDCA therapy as triple-negative breast cancer, Stage IV...In this case, the diagnosis of breast cancer was made based on these immunohistochemistry results, and treatment was initiated. Conclusion We have experienced a case of male breast cancer, which is considered to be very rare

EC was administered for 8 courses, docetaxel for 2 courses, eribulin for 4 courses, capecitabine for 3 courses, and paclitaxel + bevacizumab for 8 courses...Treatment was started with methimazole 30mg/day, hydrocortone 300mg/day, and iodine 150mg/day...As the tumor had shrunk, pembrolizumab + gemcitabine + carboplatin was resumed on the 35th day of hospitalization...As no BRCA gene mutation was found and low HER2 expression was observed, T-DXd was introduced and five courses were administered, but the disease gradually progressed, and the patient developed lymphangiectasia carcinomatosis and passed away. Thyroid dysfunction is a well-known irAE caused by pembrolizumab, but we report a case in which this developed into thyroid storm

CBDCA+PTX+Pembrolizumab (Pemb) was started in July of X, and the swelling in the left breast showed a tendency to improve...In November of X, the treatment was changed to PTX+Bevacizumab, but after completing one course, carcinomatous lymphangiopathy and multiple liver metastases appeared, and the condition further progressed, resulting in BSC 5 months after the start of treatment...&lsqb;Discussion] In the future, the importance of gene panel testing will increase for breast cancer patients, and PGPV will be detected in a certain percentage of cases. For patients with rapidly progressing disease, such as our case, it is considered essential to promptly perform genetic testing to consider the patient's treatment plan and to link this to the health management of blood relatives

We report a case of metastatic breast cancer in which the patient achieved partial response with atezolizumab plus nab-PTX, but developed colitis due to irAE, and then developed cytomegalovirus (CMV) colitis due to steroid treatment...Ganciclovir was started, and symptoms improved, and PSL was gradually tapered, and treatment was completed on day 243...In this case, CMV colitis occurred concomitantly, and it took some time before breast cancer treatment could be resumed. Although this is an irAE that occurs infrequently, it is considered necessary to pay attention to the progression of gastrointestinal symptoms and cooperate with gastroenterology from an early stage

Preoperative chemotherapy consisted of four courses of EC (90/600) therapy and four courses of docetaxel + trastuzumab + pertuzumab, followed by surgery...In considering new treatment options such as immune checkpoint inhibitors and trastuzumab deruxtecan, the results showed that PD-L1/22C3 was 10 or higher and PD-L1/SP142 was 1% or higher...In today's clinical field where drug selection is becoming more complex, the importance of treatment predictors is increasing. In this case, anti-Her2 therapy was selected as the initial treatment for HER2-type breast cancer, and after recurrence, the treatment strategy was changed to triple-negative breast cancer

In June of X year, right breast cancer cT2N3bM0 stage â…¢C Luminal B was diagnosed and neoadjuvant chemotherapy (FEC therapy, Docetaxel therapy) was performed. In December, she underwent right mastectomy and axillary dissection, and the postoperative pathology results showed a diagnosis of ypT1aN0M0 stage I. After surgery, she was administered radiation therapy (50Gy) and tamoxifen and goserelin as postoperative adjuvant endocrine therapy...In May of X+7, the internal thoracic and mediastinal lymph nodes showed a tendency for slight enlargement, so Tamoxifen was changed to Letrozole...In September, tracheal compression and recurrent laryngeal nerve paralysis due to mediastinal lymph nodes were observed, and radiation therapy (45Gy/20Fr) was performed, after which Pembrolizumab + Carboplatin + Gemcitabine administration is ongoing...A year later, metastasis was diagnosed from a slowly growing mediastinal lymph node. We report this case, including a literature review, in which it was difficult to diagnose recurrence

As residual disease was found in the postoperative pathological examination, 8 cycles (6 months) of oral capecitabine were completed as postoperative adjuvant therapy, and radiation therapy was performed on the chest wall and regional lymph nodes...Therefore, the first administration of pembrolizumab + gemcitabine + carboplatin was performed on May 2, X year...Early detection and early intervention are extremely important for irAEs, as they can occur not only during drug administration but also during drug suspension or long after the end of drug administration, can rapidly worsen, and symptoms can appear in organs throughout the body, and immunosuppressants such as steroids may be required. This case led to in-house verification and investigation of the signs and timing of irAEs, as well as how to respond when irAEs are identified, and we report this case because it became the impetus for setting up a response team

Postoperative adjuvant chemotherapy consisted of 4 courses of EC and 4 courses of docetaxel...PD-L1 testing showed SP142: positive and 22C3: positive, so atezolizumab + nab-PTX was started on October 19, 2022...Pembrolizumab + gemcitabine + carboplatin was started as third-line treatment...&lsqb;Discussion] The patient had previously been treated with atezolizumab and developed irAE, but is currently experiencing good therapeutic effects. This may be due to the effect of carboplatin, activation of T cell immunity through a pathway different from atezolizumab, and the inhibition of VEGF by Bev administered before pembrolizumab, restoring the tumor immune environment

Olaparib is scheduled to be administered for one year after surgery...After that, Risperdal was suspended on the day of administration...Conclusion We have experienced five cases of TNBC suitable for treatment with pembrolizumab. We report these cases with a literature review

PD-L1 testing was performed, and both SP142 and 22C3 met the drug administration criteria, so treatment was started with pembrolizumab + gemcitabine + carboplatin (Pem/GEM/CBDCA) from the KEYNOTE-355 trial...After surgery, it was decided to start with Herceptin + Perjeta + Docetaxel (hereinafter HPD), including anti-HER2 therapy...This time, we prioritized the treatment of the left breast cancer TNBC, which was more locally advanced, and started treatment with Pem/GEM/CBDCA, but the treatment effect was also observed for the right breast cancer, which is HER2 type. Although this experience of use was an accidental result, we hope that research on Pem will progress further and its therapeutic effect will be clarified

Pembrolizumab + GEM + CBDCA showed PD in 6 months, atezolizumab + nab-PTX showed PD in 5 months, and eribulin showed PD in 2 months, and treatment with T-DXd was started. In addition, this study was conducted after one or two chemotherapy regimens, so the effectiveness of treatment in the latter line and the effectiveness of treatment after the use of immune checkpoint inhibitors in triple-negative cases are unknown. As with HER2-positive breast cancer, treatment was able to continue while screening for nausea/vomiting and ILD, and we will continue to accumulate cases and conduct further studies

Three patients received nab-paclitaxel + atezolizumab therapy, and one received paclitaxel + pembrolizumab. Immune checkpoint inhibitors are effective for TNBC, and PD-L1 testing should be actively performed to determine suitability. In addition, since the results of SP142 and 22C3 tests can differ in PD-L1 tests, when considering immune checkpoint inhibitors for TNBC, both tests should be performed

Five cases were treated with ICI for recurrence, all of which were combination immunotherapy with atezolizumab...However, 5 cases were treated with perioperative treatment with pembrolizumab... The SP142 positivity rate was 51.5% (17/33), the 22C3 positivity rate was 58.3% (14/24), and 45.8% (11/24) were positive for both SP142 and 22C3. The specimens used for testing were, in order of SP142/22C3, 27/21 primary breast lesions, 3/1 recurrent lymph nodes, and 3/2 recurrent skin masses. The positive rates by specimen were SP142/22C3 in the order of primary breast lesions 51.9% (14/27)/66.7% (14/21), recurrent lymph nodes 66.7% (2/3)/0% (0/1), and recurrent skin masses 33.3% (1/3)/0% (0/2).

Introduction Advanced and recurrent triple-negative breast cancer (TNBC) has a poor prognosis and no therapeutic target, but in recent years, PARP inhibitors for BRCA mutation-positive breast cancer and T-DXd (trastuzumab-deruxtecan) for HER2-low-expressing breast cancer have become available. In addition, the immune checkpoint inhibitors (ICIs) atezolizumab and pembrolizumab have also been reported to significantly extend PFS in clinical trials...Conclusion Atezolizumab's efficacy and safety for advanced and recurrent TNBC were in line with clinical trials. The operation of the treatment support app is expected to become more widespread in the future, but issues such as the number of personnel required to handle the application remain a future challenge

Atezolizumab (Atezo: Tecentriq) and Pembrolizumab (Pembro: Keytruda) are currently available ICIs in the field of breast cancer...Bevacizumab + paclitaxel was used in 2 patients after PD... irAEs can occur in various organs. In addition, the time of onset is not constant, and they may appear even in cases where use has been discontinued. With this in mind, we would like to establish a system that can quickly catch abnormalities and respond quickly throughout the hospital

However, careful attention must be paid to side effects, including irAE, and it is expected that many patients will not be able to complete the original protocol. Therefore, there is room for further consideration regarding the administration of this treatment

PD-L1 testing using SP142 and 22C3 is different, and it is difficult to interpret the diagnostic results. We report these results with some literature review, including the influence of sample selection

In addition, we are currently developing and adjusting an algorithm for recognizing the regions of PD-L1-positive cell clusters, and it will be interesting to compare the results with previously reported analysis results. In addition, it will be possible to analyze the expression status of other molecular markers within the regions evaluated and identified, which is expected to further deepen the previous discussion

Low intratumoral ADC on MRI may be a predictor of PD-L1 expression in TNBC

In addition, the diagnostic agreement rate of SP142 in the primary tumor biopsy specimen, the primary tumor surgical specimen, and the metastatic/recurrent tumor in the same case was 58-67%, and the agreement rate of 22C3 was 55-84%. &lsqb;Discussion] Further consideration is needed in the future