PD-L1 negative

P1/2, N=107, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025

A similar trend was observed when comparing PD-L1 expression in TIMCs. However, no differences in overall survival for PD-L1-positive pRCC patients with compared to PD-L1-negative patients were observed in tumor cells or TIMCs.

Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005). In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.

P2, N=110, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Apr 2027 --> Apr 2029 | Trial primary completion date: Apr 2024 --> Apr 2026

Chemoradiotherapy (CRT) followed by consolidation of immune checkpoint inhibitors (ICIs), such as durvalumab or pembrolizumab, for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression <1% remains a topic of controversy. The findings of the present study highlighted that the benefits of CRT followed by consolidation of ICIs were higher compared with CRT alone in patients with unresectable, locally advanced NSCLC and PD-L1 expression <1%. Consolidation of ICIs after CRT would provide greater benefits for locally advanced NSCLC patients with PD-L1 expression ≥1% compared with those with PD-L1 expression <1%.

Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

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

Survival is associated with menopausal status and family history. No association was found between survival and PDL1 as well sidedness in our study.

For patients exhibiting positive PD-L1 expression, a negative correlation was observed between PD-L1 expression and both serum iron and transferrin levels (r = -0.465, P=0.003; r = -0.447, P=0.005), and a positive correlation was noted between PD-L1 expression and ferritin levels (r=0.393, P=0.015). We conclude that in In patients with advanced non-small cell lung cancer, serum iron and transferrin levels can serve as partial predictors of PD-L1 expression; among those positive for PD-L1, a significant association exists between indicators of iron metabolism and PD-L1 expression.

Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy.

In conclusion, our deep learning algorithm demonstrates promise in detecting PD-L1 expression at a cellular level and exhibits favorable agreement with pathologists in quantifying the tumor proportion score (TPS). We publicly release our models for use via the Grand-Challenge platform.

With positive HER-2 status, off-label trastuzumab/docetaxel was initiated in an individual healing attempt, during which the pulmonary metastases showed clear progression. After 57 cycles of nivolumab, the patient presents with partial remission and in good condition. We report, for the first time, a robust response of metastatic SDC to checkpoint inhibition with nivolumab without additional radiotherapy.

P2, N=120, Suspended, Vanderbilt-Ingram Cancer Center | Recruiting --> Suspended

The results of the biodistribution showed that the MDA-MB-231 tumor uptake of 64Cu-NOTA-Durva was much higher than 64Cu-NOTA-IgG (a nonspecific radiolabeled IgG). In Conclusion, 64Cu-labeled Durvalumab PET/CT imaging offers a promising, noninvasive approach to evaluate tumor PD-L1 expression.

Some immunotherapy regimens have better efficacy than traditional chemotherapy in patients with negative PD-L1 expression. Patients with NSCLC and negative PD-L1 expression can receive better survival benefits under some immunotherapy types, and these may represent a better treatment option for this relatively small patient population.

PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.

This systematic review and meta-analysis suggests that PD-L1 expression is associated with improved ORR, OS, and PFS for patients with mUC who receive ICIs, but it is unlikely to be useful as a predictive biomarker. Developing predictive biomarkers is essential to select patients most likely to benefit from ICIs and avoid toxic effects and financial burden with these agents.

This study indicates that an early 30-minute dynamic FDG-PET acquisition appears to be sufficient to provide quantitative images with good-quality and accurate Ki values for the assessment of lung lesions and prediction of PD-L1 expression. Protocols with a shortened early 30-minute acquisition time may be considered for patients who have difficulty with prolonged acquisitions to improve the efficiency of clinical acquisitions.

Our findings suggest that AR is the promising target for UTUC treatment, especially in PD-L1-negative cases.

ER downregulates PD-L1 in type I EC. The findings of this study can be used as reference data and as the basis for further research, especially investigations of the prognostic and immunotherapeutic value of ER and PD-L1 expression in type I EC.

KRASm are associated with worse overall survival in PD-L1 negative NSCLC; however, this association is largely driven by comutations with STK11 and KEAP1, which are enriched in PD-L1 negative tumors.

P1, N=140, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Aug 2024 --> Aug 2025

In conclusion, the expression of PDL-1, and with it, of an inhibitory factor of the cellular immune response, correlates with a decrease in thromboembolic events in patients with gastric cancer, which could indicate the crucial role of the immune response in which thromboembolic events occur.

In our study, PD-L1 expression was significantly higher in squamous cell carcinomas and lower in adenocarcinomas, and was positively associated with MET and KRAS mutations, as well as the wild-type EGFR gene state. Nonetheless, additional studies are needed to further validate those associations and determine the clinical significance for immune checkpoint inhibitors of these factors.

Material/Methods It was a retrospective single-center analysis involving OC and PX patients who underwent radical RT (66Gy prescribed to the primary tumor, given in 30 fx/6 weeks) with or without concurrent chemotherapy (Cisplatin 100 mg/m2 i.v. every three weeks or 40 mg/m2 i.v weekly)...In univariate analysis we did not find any predictive factors for RT response. The main limitation of our study was very small group sizes.

1. Ours is the first study to demonstrate that SP263 and E3L1N can reliably be used to evaluate PD-L1 in PCs as there is good concordance with the reference clone 22C3. 2.

Our study failed to show significant associations between PD-L1 IHC and HRD parameters. TMB score was positively associated with LOH-high, but not HRR gene mutation. Independently evaluating these markers needs to be considered to select patients for targeting therapies.

About half of the breast SCCs exhibited high sTILs and positive PD-L1 expression, which indicated the potential opportunity for immunotherapy. Genomic profile revealed clinically meaningful alterations that might guide targeted treatment decisions in SCC patients.

AI-powered IHC quantification identified more PD-L1 positive cases who may respond better to immune therapy and may have prolonged overall survival. This finding suggest that AI-powered scoring could have greater clinical relevance compared to pathologists' manual scoring.

In conclusion, the evaluation of CTCs and CTC PD-L1 suggested that undetectable CTCs at 6 months of NSCLC treatment are associated with a good prognosis. In addition, negative CTC PD-L1 expression may change to positive CTC PD-L1 expression in line with disease progression, and this may be indicative of poor prognosis.

P3, N=953, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024

CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.

P2, N=90, Active, not recruiting, Gilead Sciences | Recruiting --> Active, not recruiting | N=144 --> 90

The prevalence and types of EGFRm were similar between early stage and advanced stage NSCLC. While lower prevalence of PD-L1 expression was found in early stage disease. Patients with both EGFRm and PD-L1 expression had poorer outcome. Thus PD-L1 expression would be one of the prognostic factor in EGFRm patients. Validation of the predictive score should be performed in a larger cohort.

Second-line PD-1 inhibitor combined with albumin paclitaxel and apatinib showed certain efficacy and safety in patients with mGC.

The role of LAG-3 expression on circulating NK cells, as well as the expression of LAG-3 ligands on tumor cells and the early modulation of circulating cytotoxic CD4+ T cells warrant further investigation as exploitable predictive biomarkers for dual PD-1 and LAG-3 blockade.Trial registration: NCT02460224. Registered 02/06/2015.

Patients with RET fusion positive NSCLCs may not benefit from ICI based regimens and therefore should not be treated with ICIs in clinical practice.

Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.

Analysis of progression-free survival (PFS) after the first line of treatment with immune checkpoint inhibitors (ICIs) in 30 pts with stage IV KRAS-mutated NSCLC and high PD-L1 showed a trend favoring patients presenting a co-mutation (mPFS 13.7mo KRAS co-mutated vs. 3.6mo in KRAS only; HR 0.26; CI 95% 0.09-0.070; p=0.19). Conclusions These findings emphasize the importance of further exploring PD-L1 role in KRAS mutated patients, especially by taking into account accompanying mutations in other genes evaluated by NGS.

Immature OS analysis (IA1) suggested a directionally favorable benefit with the addition of pembrolizumab to CP in both the dMMR and pMMR EC cohorts despite (%***pending) crossover to immunotherapy at progression.  Incorporation of Pembrolizumab resulted in a significant improvement in PFS irrespective of PD-L1 expression levels.