PD-L1 negative

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.

The present meta-analysis confirmed that the benefit of PD-1 blockade in GEA patients is related to PD-L1 CPS, with increased benefit observed for higher CPS cut-offs and no OS benefit in the CPS <1 subset. Overall, data indicate that PD-L1 CPS ≥5 could represent an acceptable cut-off to optimize the risk/benefit ratio of such agents. Our data suggest a potential clinical benefit of immunotherapy in selected patients within the CPS 1-4 population which needs further investigation.

His resistance to trastuzumab was overcome after the addition of a PD-1 inhibitor, after which he received a durable response for more than 8 months. In HER2-positive, PD-L1-negative metastatic GC, the addition of PD-1 inhibitors after first-line chemotherapy and trastuzumab treatment resistance may be an option.

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.

P1, N=140, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Aug 2025 --> Mar 2026

The results indicate a higher response rate to anti-PD-1 therapy in patients positive for both PD-L1 and PD-L2, with PD-L2 status independently predicting progression-free survival (PFS) with pembrolizumab treatment. Furthermore, &lsqb;68Ga]Ga-HN11-1 PET imaging demonstrates specificity in assessing PD-L2 status. Overall, we confirm the correlation between high PD-L2 expression and favorable PFS in NSCLC patients post anti-PD-1 therapy and highlight the promising potential of &lsqb;68Ga]Ga-HN11-1 as a specific tracer for PD-L2 in preclinical and initial human trials.

More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics. https://inplasy.com/inplasy-2023-3-0064/ identifier, INPLASY202330064.

Thus, we initiated the administration of dexamethasone (3.3 mg/day). Pembrolizumab may be effective against G-CSF-producing NSCLC with high PD-L1 expression. Corticosteroids seemed to inhibit inflammation induced by the tumor, and exert the efficacy of pembrolizumab.

PDL-1/TILS and PDL-1/TC are independent prognostic factors in OSCC and PDL1-/TILS has an important role.

A modest response to pembrolizumab monotherapy was detected in the mTNBC patients. Furthermore, a better outcome from pembrolizumab treatment may be predicted by PD-L1-- positive status, non-liver/lung metastases, combination therapy, and first-line immunotherapy. Pembrolizumab, in combination with chemotherapy, may be more beneficial for patients whose tumors are PD-L1 positive.

This situation suggests that breast surgeons, in particular, should conduct a thorough physical examination and, if necessary, re-radiological examination before surgery on patients for whom surgery is decided after diagnosis. Being careful in this regard may increase the number of SR in BC cases and allow molecular investigations on living tissue samples to reveal the underlying mechanism.

OSCC arising in never-smokers/never-drinkers exhibit heightened PD-1/PD-L1 signaling, suggesting potential efficacy of immune checkpoint therapy in this subgroup of tumors.

Recently, attention has also been drawn to the lung microbiota and tumor microbiota in the context of lung cancer, with reports suggesting that increased diversity in these microbial communities may correlate with the efficacy of ICI therapy. However, none of these findings alone provide sufficient evidence as standalone biomarkers, necessitating future research to advance from both the host environment, including the gut microbiota, and the microenvironment of the tumor site, such as the lung and tumor microbiota.

Accordingly, we achieved a complete response in a radiotherapy (RT) and chemotherapy (CT)-refractory patient with locally recurrent lacrimal gland (LG) ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters, especially in "immune-cold" cancer types.

Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

P2, N=92, Terminated, Gilead Sciences | Active, not recruiting --> Terminated; Sponsor decision to terminate study.

Immuno-chemotherapy is a first-line optional treatment strategy in addition to targeted therapy for NSCLC patients with primary METamp. Foxp3-negative expression better predicts the near-term efficacy of immunotherapy.

P2, N=24, Not yet recruiting, University of Alabama at Birmingham | Initiation date: Oct 2024 --> Jan 2025

Consequently, IRE1α RNase inhibitor plus taxane converts PD-L1-negative, ICI-unresponsive TNBC tumors into PD-L1high immunogenic tumors that are hyper-sensitive to ICI. We reveal IRE1α as a cancer cell defense mechanism that prevents taxane-induced danger signal accumulation and pyroptotic cell death.

P3, N=540, Recruiting, Gilead Sciences | Trial completion date: May 2027 --> Jul 2028 | Trial primary completion date: May 2027 --> Jul 2028

In addition, compared with PD-L1-negative yolk sac tissue, dysgerminomas/seminomas with high PD-L1 expression are associated with more genetic alterations and a better prognosis. Our findings will contribute to the knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumor patients and the risk factors for resistance mediated by tumor microenvironment cells.

FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.

P2, N=30, Recruiting, Elizabeth Buchbinder, MD | Trial primary completion date: Sep 2024 --> Dec 2024

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.

Ethics Approval Tempus AI, Inc. has been granted an IRB exemption (Advarra Pro00072742) permitting the use of de-identified clinical, molecular, and multimodal data in order to derive or capture results, insights, or discoveries.Download figure Open in new tab Download powerpoint Abstract 188 Figure 1

The KEYNOTE-B84 study (NCT04815720) evaluated the safety and efficacy of pepinemab in combination with pembrolizumab as a first-line treatment for immunotherapy-naïve patients with R/M HNSCC. Biomarker studies conducted in patients with surgically resectable metastatic melanoma (NCT03769155) and HNSCC (NCT03690986) received neoadjuvant treatment with pepinemab/nivolumab/ipilimumab combinations compared to nivolumab or ipilimumab alone...Increased density and maturity of lymphoid aggregates correlated with disease control and longer progression-free survival (PFS). Conclusions Pepinemab, a Semaphorin 4D (SEMA4D) blocking antibody, in combination with ICB converts 'Cold' tumors to 'Hot' by inducing organized lymphoid aggregates.

Here, we describe the unique case of a 50-year-old self-experimenting female virologist with locally recurrent muscle-invasive breast cancer who was able to proceed to simple, non-invasive tumour resection after receiving multiple intratumoural injections of research-grade virus preparations, which first included an Edmonston-Zagreb measles vaccine strain (MeV) and then a vesicular stomatitis virus Indiana strain (VSV), both prepared in her own laboratory. The patient completed one-year trastuzumab adjuvant therapy and remains well and recurrence-free 45 months post-surgery. Although an isolated case, it encourages consideration of oncolytic virotherapy as a neoadjuvant treatment modality.

MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

After joint clinical feature modeling, the AUC and accuracy of predicting PD-L1 positive for PET/CT were 0.96 ± 0.00905 and 0.950 ± 0.0250, respectively. This study combines the features of 18F-FDG PET/CT images with clinical features using deep learning to predict the expression of PD-L1 in NSCLC, suggesting that 18F-FDG PET/CT images can be conducted as biomarkers for PD-L1 expression.

P2, N=92, Active, not recruiting, Gilead Sciences | Trial completion date: Jan 2025 --> Oct 2024

Regarding subgroup analyses, there was significant benefit among patients with negative PD-L1 expression (HR 0.76, 95% CI 0.64-0.90), those who received prior NAC (HR 0.69, 95% CI 0.52-0.91), and patients with lower tract (HR 0.71, 95% CI 0.55-0.92) but not upper tract disease (HR 1.21, 95% CI 0.87-1.68). This pooled analysis of DFS and safety provides support for ICI utilization in the setting of high-risk resected MIUC.

The 7-year analysis of adjuvant therapy with pembrolizumab demonstrated a sustained improvement in the long-term RFS, DMFS and PRFS2 compared with placebo in patients with resected stage III melanoma.

PD-L1 positivity emerged as an independent risk factor for RFS in patients with EGFR-mutant resected lung adenocarcinoma. These findings may provide valuable insights into the prognostic impact of PD-L1 expression and guide the implementation of postoperative adjuvant therapy in this patient population.

Immunotherapy has shown poor efficacy in the unselected population of HG-GEP-NENs because the immune microenvironment landscape was scant in HG-GEP-NENs at transcriptomic analysis and PD-L1 expression was absent. Thus, there is a great need to identify subsets of HG-GEP-NENs responsive to immunotherapy approaches. The present results addressed GEP-NECs with high proliferation index as sensible candidates to immunotherapy due to the enrichment in TMB-high and MSI coupled with higher CD4+ and CD8+ T cell expression.

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.

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.

ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.

Importantly, nonresponder patients with high prediction score turned out to have high CTLA4 expression, which suggested that neoadjuvant CTLA4 combination therapy might be effective for these patients. Our data and analysis results provide valuable insights into developing biomarkers and strategies for treating LUAD patients using immune checkpoint inhibitors.

Pembrolizumab was added to cycle three of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She had progression on this regimen and was transitioned to tisotumab vedotin; however, ultimately opted to proceed with hospice secondary to failure to thrive.Case 2A 36-year-old woman with history of an abnormal pap smear in pregnancy and initial biopsy demonstrating endocervical adenocarcinoma, mucinous type...This is the first case report describing these inconsistencies. Etiologies of and outcomes related to the discrepant expression of PD-L1 should be further studied.

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.

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).

Baseline TCR metrics, particularly convergence, evenness, and TOP1% CS, demonstrate robust predictive value for CPR and survival in locally-advanced NSCLC patients undergoing perioperative nivolumab plus chemotherapy, warranting further investigation in larger cohorts.