Active clinical trials for "Carcinoma, Non-Small-Cell Lung"

This project is to assess the immunogenicity, safety and overall survival impact of intramuscular injection of trivalent influenza vaccine in non-small cell lung cancer (NSCLC) patients with PD-1/PD-L1 inhibitor treatment.

The investigators will obtain a cohort of patients from multiple large cancer centers in China and try to unravel the efficacy of "radiotherapy combined with EGFR-TKI", which may provide some evidences for the treatment of stage III-inoperable NSCLC.

The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor（EGFR-TKI） osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

We hypothesized that TGR could serve as an early predictor of outcomes for aNSCLC patients undergoing immune checkpoint inhibitors (ICIs). A retrospective analysis was conducted to investigate the association of TGR with response and long-term survival of aNSCLC patients undergoing ICI therapy.

Currents strategies for cancer diagnosis consist of the extraction of a solid tissue from the affected area. This sample enables the study of specific biomarkers and the genetic nature of the tumor. However, the tissue extraction is risky and painful for the patient and in some cases is unavailable in inaccessible tumors. In addition, cancer is a dynamic disease and during the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumour might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumour-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity). To overcome these drawbacks, new alternatives are rising up, such as liquid biopsy. A liquid biopsy is the analysis of biomarkers in a non-solid biological tissue, mainly blood, which has remarkable advantages over the traditional method; it has no risk, it is non-invasive and painless, it does not require surgery and reduces cost and diagnosis time. Of the various circulating biomarkers, circulating tumor cells (CTCs) have particularly opened new windows. Circulating tumor cells (CTCs) are released into the bloodstream from primary cancer, metastasis, and even from a disseminated tumor cell reservoir. CTCs may ideally replace tissue biopsies in the prediction and monitoring of therapeutic responses and tumor recurrence. CTCs can be used to guide therapeutic cancer management and serve as drug targets. There are a wide range of instruments and methods for capturing, enriching, and enumerating CTCs. However, none of them is considered optimal. To improve the purity of CTCs, the study consortium has developed a cutting-edge microfluidic device (LUTON) to reduce leukocytes contamination while preserving CTCs viability. The added-value of the study innovation has been validated on clinical cell lines. The aim of this study is now to determine the performance of the device using patients' blood samples. For this purpose, CTCs from non-small cell lung metastatic cancer patients will be isolated using ClearCellFX1 before injection into the LUTON workflow. Collected cells will then be either growth in vitro or in ovo and the added value of this extra step of purification determined.

This is an external control, observational, retrospective study designed to compare clinical outcomes for pralsetinib compared with best available therapy for patients with RET-fusion positive advanced NSCLC.

Inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are effective therapies for metastatic NSCLC lacking sensitizing EGFR or ALK mutations. First-line combination regimens that include a PD-1 or PD-L1 inhibitor may maximize the chance of response and lead to prolonged survival. PD-L1 expression is the only validated predictive biomarker for selecting pembrolizumab treatment. However, it is far from being the ideal biomarker and its role in predicting efficacy from ICPIs remains undefined due to conflicting results from randomized clinical trials. The selection of patients most likely to benefit from immunotherapy is crucial in order to avoid exposure to potentially toxic and ineffective drugs as well as to prevent inappropriate allocation of health resources. Further studies are clearly needed to better understand the mechanism of action of immunotherapy in vivo thus allowing the identification of other predictive biomarkers. Therefore, our research team intends to explore advanced non-small cell lung cancer treated with immune checkpoint inhibitors, by combining the evaluation criteria of solid tumor efficacy evaluation criteria (RECIST1.1), clinical pathological characteristics of patients, and dynamic monitoring of peripheral blood molecular biological markers, finding the correlation with the efficacy of immunotherapy, establish a detection mode for selecting patients with clinical benefits.

Therapeutic antibodies that block the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) pathway have revolutionized immuno-oncology by inducing robust and durable responses in patients with various cancer including advanced non-small-cell lung cancer (NSCLC). However, these responses only occur in a subset of patients, even in case of PD-L1 overexpression. Elucidating the determinants of response and resistance but also of severe immune-mediated adverse events is key to improving outcomes and developing new treatment strategies. Biomarkers that predict immune checkpoint inhibitors efficacy and toxicity are urgently needed and could emerge from characterization of tumor microenvironment. The purpose of PREDICTION project is to elucidate response and toxicity predictive immunophenotypic signatures using a new in situ multiplexed strategy with imaging mass cytometry Hyperion. Patients treated with anti-PD-1 pembrolizumab will be selected on their response and toxicity profiles. Then, tumor samples will be analysed with Hyperion technology, allowing delineation of cell subpopulations and cell-cell interactions, highlighting tumor heterogeneity and to determine correlations between response and toxicity features. The number of co-analysable markers enables global vision on the same tissue section. A better understanding of the tumor microenvironment complex system will lead to discover new predictive biomarkers potentially transferable to current practice.

VeriStrat® is a pretreatment blood-based test correlated with clinical outcome after EGFR-TKI therapy in non-small cell lung cancer (NSCLC) patients. The investigators hypothesis is that VeriStrat could be also employed as a biomarker of benefit from treatment with standard chemotherapy regimens in first line NSCLC patients.

Modern anti-cancer treatments are focused on development of molecular based therapies i.e. specific treatments targeted against underlying biological processes. There is still much to learn about the biology of cancer, especially in tumours such as colorectal and lung cancer where it is likely multiple heterogenous signaling pathways are responsible for progression of disease. This project aims to evaluate circulating tumour cells (CTCs) as a surrogate biomarker for tumour characteristics and to determine how they may used to identify new targets for therapeutic agents. Their use could be applied to diagnosis of cancer, prediction of response to therapies and prognosis, ultimately across a broad range of tumour types. Currently the only way to investigate molecular features of a cancer is through procurement of an invasive tumour biopsy that is often difficult to obtain, often results in insufficient material and is unpleasant for the patient. A blood-based test would provide a much more practical and patient friendly alternative. The enumeration and molecular characterisation of CTCs has the novel potential of being a "virtual biopsy" of the tumour and offers the opportunity for immediate therapeutic decisions (eg. if the tumour develops a therapy resistant genotype while on treatment). CTCs have been known to circulate in bloodstream of cancer patients for many years and are known to lead to cancer metastases. They have been very difficult to detect, up until recently, due to the complexity of the metastatic process and detecting relatively small numbers of CTCs amongst billions of red and white blood cells. However, technology has moved on dramatically in the last few years. The FDA approved CellSearch platform (Veridex, NJ) can isolate and enumerate CTCs based on the immunomagnetic capture of EpCAM (epithelial cell adhesion molecule) positive cells. Several studies have recently demonstrated the value of CTC enumeration in reflecting prognosis and predicting early response to systemic chemotherapy. For example, in a study comprising 456 patients with metastatic colorectal cancer starting a new line of therapy, patients with =3 CTCs per 7.5 ml blood at baseline had shorter progression free survival (PFS) and overall survival (OS) compared to those patients with < 3CTCs at baseline (PFS 4.5 versus 7.9 months P=0.0001; OS 8.5 versus 19.1 months P=0.0000 respectively). Overall survival for patients converting to or maintaining CTCs =3 within a few weeks of commencing systemic therapy remained worse than for those patients maintaining CTC counts < 3 per 7.5ml blood. Similar results have been reported in patients with breast and hormone refractory prostate cancer (HRPC). These studies have led to FDA approval of the CellSearch system as an adjunct to monitoring patients with these 3 tumour types. The CellSearch platform, however, does not allow for the downstream DNA analysis of captured cells and the ferroparticle-coated CTCs are non-viable. Furthermore, this platform is a multi-machine, multi-kit system that is laborious (typical 3-7 days turnover time), expensive (USD 650), and subject to operator variance. In this protocol, the investigators propose for the first time, an automated, fully quantitative system for isolation and enrichment of CTCs. The key differentiating feature of our novel CMOS system is the electrochemical identification and counting of tumour cells using a high density electrode array with associated electronics for addressing the electrodes. This leads to a standardized assay for tumour cells with a shorter turnover time and without the need of a skilled operator. This system also holds the potential for allowing the molecular characterization of CTCs. This study aims to enumerate CTCs using a novel CMOS technology in patients with metastatic cancer who are scheduled to receive palliative chemotherapy, and to correlate CTC number with clinical outcome. In Part I of the study, the investigators will recruit 10 patients with metastatic NSCLC and 10 patients with metastatic CRC in order to assess the feasibility of CTC enumeration in patients. In particular, the investigators aim to establish whether CTCs are detectable using the novel CMOS technology in patients with metastatic cancer. In Part II of the study, the investigators will recruit 21 patients with metastatic NSCLC and 89 patients with metastatic CRC in order to compare CTC counts as determined by the CMOS technology with CTC counts as determined by the CellSearch platform. Blood samples will be collected at a single time point prior to the start of palliative chemotherapy. CTC numbers will be correlated with clinical outcome in all evaluable patients. The investigators hypothesize that CTC enumeration by a novel CMOS technology is non-inferior to CTC enumeration by the CellSearch platform in patients with advanced solid malignancies.