PD-L1 negative

We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular-pathological, clinical, and prognostic analysis correlating with prognosis.

PD-L1 expression in pre-treated EGFR T790 M + lung adenocarcinoma is not predictive of osimertinib efficacy, as demonstrated by in vitro, xenograft, and clinical case studies.

P2, N=70, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

The combination of Tislelizumab and Sorafenib demonstrates promising antitumor activity in the first-line treatment of hepatocellular carcinoma, with a relatively high objective response rate (ORR) and acceptable safety profile. Baseline CTC PD-L1 positivity can serve as a predictive marker for selecting hepatocellular carcinoma patients for PD-1/PD-L1 blockade therapy, and dynamic measurement of CTC changes can be used to monitor treatment efficacy.

P2, N=19, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Oct 2026 --> Feb 2027

Unfortunately, the patient progressed rapidly during maintenance therapy when cadonilimab was replaced by sintilimab, the monoclonal antibody against PD-1, indicating the more powerful anti-tumor activity of dual blockade immunotherapy. To conclude, cadonilimab offers a promising and effective therapeutic approach for R/M CC. Notably, HER-2 is also expected to be a new reference target for cadonilimab therapy.

A comprehensive evaluation of multiple tumor biomarkers should be considered in NSCLC patients. Pembrolizumab monotherapy could benefit NSCLC patients with negative driver genes, PD-L1 negative, a high tumor mutational burden, and positive tumor-infiltrating lymphocytes.

He was given sintilimab and anlotinib as first line treatment...Subsequently, the second line regimen was modified to etoposide and cisplatin (EP) combined with anlotinib and penpulimab...Notably, the patient's progress-free survival (PFS) exceeds 7 months and the overall survival up to 12 months. Our case implies that a combination of chemotherapy, anlotinib, and penpulimab might offer a promising therapeutic approach for PD-L1-negative thoracic SMARCA4-UT.

DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. The FOXL2 mutation is less common in these tumors and is mutually exclusive with the DICER1 mutation.

The study concluded that the PD-L1 expression scoring system effectively discriminates between patients with breast cancer in terms of the degree of benefit they may attain from ICIs. Patients with little or no PD-L1 expression experienced a diminished therapeutic benefit from ICIs.

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.

BRCA mutation and PD-L1 positivity are higher in HER2-negative TNBC. Our study revealed that HER2-negative breast cancer has more basal-like clinicopathologic features, while HER2 Low TNBC has non-basal features.

Neoadjuvant treatment in both study arms consisted of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant CTX (12 x Carboplatin/Paclitaxel q1w followed by 4x Epirubicin/Cyclophosphamide q3w), in arm A preceded by an Atezolizumab monotherapy window of 840 mg once two weeks prior to initiation of combination therapy. In this analysis, the association between PD-L1 (IC) status and pCR rates could be reproduced in a subgroup of patients with =/> cT2 and/or N+ tumors. These results are in line with exploratory results of the NeoTRIP trial and the IMPASSION031 trial demonstrating an association of PD-L1 status with pCR rates after neoadjuvant Atezolizumab + chemotherapy in patients with high risk eTNBC similar to the population in this subgroup analysis. Our analysis in the largest group of patients with high risk eTNBC treated with neoadjuvant Atezolizumab + chemotherapy published to date demonstrated a significant association of PD-L1 status and pCR rates.

Further, these results feed into the growing body of research demonstrating CPS as a precise and reproducible scoring algorithm across multiple tumor types. In addition to strengthening confidence in the reliability of the device and scoring algorithm, these consistent results have a potential impact on breast cancer treatment; however, additional studies are required to confirm.

Neoadjuvant treatment in both study arms consisted of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant CTX (12 x Carboplatin/Paclitaxel q1w followed by 4x Epirubicin/Cyclophosphamide q3w), in arm A preceded by an Atezolizumab monotherapy window of 840 mg once two weeks prior to initiation of combination therapy. To our knowledge our analysis is the largest prospective dataset regarding patients with eTNBC and low tumor burden treated with neoadjuvant chemotherapy and an immune checkpoint inhibitor. No significant differences were seen between treatment arms although numerically PD-L1 positive patients showed increased benefit from the immune therapy window. pCR rates were higher compared to the overall study population which may be attributed particularly to smaller tumor size.

This study showed in TN, TROP2 expression is notably higher in PD-L1 positive and TIL-high samples, and no significant correlation was found between TROP2 expression and inflammatory markers in the overall HER2-negative breast cancer. It provides the insight of the combination therapy of ICI and ADC targeting TROP2 in TN. Further research is warranted to explore these associations and develop personalized treatment approaches.

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.

Background Neo-CheckRay (NCT03875573) demonstrated high rates of pathological complete response (pCR) after immune-modulating stereotactic body radiation therapy (iSBRT) to the primary BC in combination with the anti-PD-L1 durvalumab (durva) in high-risk early-stage luminal BC...Pts were randomized 1:1:1 to ARM 1: paclitaxel q1w x12 with iSBRT at week 4 (3x8 Gy targeting the primary tumour, avoiding lymph nodes and normal breast tissue), followed by dose-dense epirubicin/cyclophosphamide q2w x4; ARM 2 : arm 1 + durva q4w x5; and ARM 3 : arm 1 + durva + oleclumab (anti-CD73) q2w x4 then q4w x3...Table: 2O All Arm 1 Arm 2 Arm 3 n 135 45 45 45 pts, % B: PD-L1 negative* 58.5 57.8 57.8 60.0 W6: no tumor 32.2 13.5 46.3 34.9 W6: TILs increase 14.0 16.2 12.2 14.0 W6: PD-L1 IC increase 42.7 31 48 48 pCR rate, % All pts 28.9 17.8 33.3 35.6 B: PD-L1 negative* 24.0 3.8 34.6 33.3 W6: no tumor 48.7 40.0 47.4 53.3 W6: TILs increased 17.6 0.0 20.0 33.3 W6: PD-L1 IC increased 24.0 0.0 46.0 40.0 TILs: pts, % B: TILs ≥ 1% 51.5 51.2 50.0 53.3 W6: TILs ≥ 1% 26.8 28.1 27.3 25.0 PD-L1: pts, % B: PD-L1 IC ≥ 1% 57.0 57.8 57.8 55.6 W6: PD-L1 IC ≥ 1% 70.5 48.3 85.7 82.1 B: PD-L1 TC ≥ 1% 22.2 24.4 17.8 24.4 W6: PD-L1 TC ≥ 1% 29.9 13.8 42.9 37.0 B: PD-L1 CPS ≥ 1% 39.3 37.8 40.0 40.0 W6: PD-L1 CPS ≥ 1% 54.5 37.9 66.7 63.0 B, baseline; pts, patients; W6, week 6. *Stratification factor.Conclusions In pts treated with iSBRT+durva, PD-L1 increase or absence of tumor at W6 is associated with higher pCR rate at surgery.

Table: 152P RECIST 1.1 N=31 iRECIST N=31 Complete response (%) 9.7 9.7 Partial response (%) 25.8 29.0 Stable disease (%) 22.6 25.8 Progressive disease (%) 41.9 35.5 Overall Response Rate (ORR)* (%), &lsqb;95% CI] 35.5, &lsqb;19.2-54.6] 38.7, &lsqb;21.8-57.8] Disease Control Rate (DCR) (%), &lsqb;95% CI] 58.1, &lsqb;39.1-75.5] 64.5, &lsqb;45.4-80.8] *10/11 responses confirmed by RECIST 1.1 and 11/12 by iRECIST.Conclusions E + P leads to high ORR and DCR in a CPS negative pt population, which is typically unresponsive to P alone. Further late-stage clinical investigation is warranted for E+P in this disease setting.

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

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

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.