14662 results for "PLOS+ONE+Pennsylvania+German+ACS+language+code+pdc+open+access+study"

in 25.96 milliseconds.

• Total RNAseq in the sporadic ALS and healthy control motor cortex

  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons leading to progressive muscle weakness, wasting and paralysis that result in death within a few years from disease onset. In order to characterize RNA alterations in ALS, total RNAseq was performed in the ALS motor cortex, which is an early and vulnerable region in ALS.

  Study EGAS00001004286

• Whole-exome sequencing of PTC, benign nodule and normal tissues in 28 patients

  In order to comprehensively investigate the genetic relationship between PTC tumors and benign nodules, we totally collected 127 fresh-frozen biopsies samples from 28 patients with concurrent thyroid benign nodule and PTC (n=20) or simple benign nodule (n=8). We carried out whole-exome sequencing on all the 127 biopsies samples and RNA-sequencing in total of 40 samples.

  Study EGAS00001002312

• The evolution of adult T-cell acute lymphoblastic leukemia

  We profile the whole-genome of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies. Concretely, samples were taken at the time of diagnosis (primary), at time of remission (used as control) and at recurrence of the malignancy after treatment (relapse). The libraries were sequenced on HiSeq 4000 or NovaSeq 6000 (Illumina) with a paired-end read length of 2x151bp.

  Study EGAS00001004750

• Analysis of Loose Ends in Cancer Genome Structure

  Short-read sequencing (SRS) forms the basis of our understanding of cancer genome evolution, yet it is widely thought to be inadequate for detecting structural variants (SVs). To understand the nature of cancer SVs missed by SRS, we introduce the concept of "loose ends" - sites of missing rearrangements revealed by balancing copy number (CN) across the genomic intervals and adjacencies of a genome graph.

  Study EGAS00001007324

• We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.

  We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.

  Study EGAS00001002719

• Capture Hi-C on Hodgkin lymphoma cell line L-428

  In situ promoter capture Hi-C on Hodgkin lymphoma cell line L-428 in experimental triplicates. Hi-C libraries were prepared as previously described (Orlando et al., 2018, https://currentprotocols.onlinelibrary.wiley.com/doi/pdf/10.1002/cphg.63). Promoter capture was based on 32,313 biotinylated 120-mer RNA baits (Agilent). Hi-C libraries were sequenced using Illumina HiSeq 2000 technology. The files are in FASTQ format.

  Study EGAS00001003032

• Imaging metabolic heterogeneity in breast cancer using hyperpolarized 13C-MRI

  Higher 13C-lactate labeling was seen in the more aggressive tumors, including all triple negative breast cancers. There was a significant correlation between lactate labeling and expression of the monocarboxylate transporter (MCT1), which mediates tumor cell pyruvate uptake, and a weaker correlation with expression of LDHA, which catalyzes label exchange between the injected pyruvate and the endogenous lactate pool.

  Study EGAS00001004118

• Ancient nuclear genomes enable repatriation of Indigenous human remains

  For many decades Indigenous people, including Native Americans and Aboriginal Australians, have fought for their return of their ancient people. By sequencing ten ancient nuclear genomes of Aboriginal Australians and 27 mitogenomes from ancient pre-European Aboriginal Australians (up to 1,540 yr BP) of known provenance we demonstrate the feasibility of successfully identifying the geographic origins of unprovenanced ancestral remains using genomic methods.

  Study EGAS00001003359

• 16S rRNA gene amplification and maternal factors

  Human breast milk contains a diverse community of bacteria but factors that produce variation in the breast milk microbiome are largely unknown. We evaluated if 1) maternal factors including breastfeeding practices modified the diversity and abundance of bacterial communities in breast milk and 2) if subclinical mastitis (SCM), an asymptomatic inflammatory condition occurring during lactation, induced a distinctive microbiota signature.

  Study EGAS00001003044

• Molecular profiling of DLBCL patients treated in the HOVON84 trial

  Using a comprehensive NGS assay for simultaneous screening of mutations, copy number alterations, and translocations, 5 biology-based risk profiles could be reproduced in a Dutch DLBCL population and validated for outcome prediction. This approach will enable application as a diagnostic tool to select DLBCL patients for risk adapted treatment and help to develop biomarker-driven clinical trials for personalized medicine.

  Study EGAS00001003949

• Whole-exome sequencing of extranodal NK/T cell lymphoma

  Extranodal NK/T cell lymphoma (ENKTCL) is an aggressive Epstein-Barr virus-associated T/NK neoplasm that predominantly affects Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients including whole-exome sequencing (N = 16). Commonly deregulated gene pathways in ENKTCL included epigenetic modifiers followed by human leukocyte antigen (HLA) and related genes and JAK-STAT pathway.

  Study EGAS00001004357

• Illumina HiSeqX whole genome sequence data on 58 samples including 54 with known HTT triplet repeat expansions (2 premutation and 52 full expansions)

  Whole genome sequence (WGS) data was generated on 58 samples with validated repeat lengths for the CAG repeat associated with Huntington disease, These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, WGS data.

  Study EGAS00001002593

• Analysis of transcriptomic profiles from affected and recovered muscle biopsies from children with reversible infantile respiratory chain deficiency.

  All patients carry mitochondrial mutation m.14674T>C but not must also carry mutations in related genes such as TRMU and EARS2. Analysis compares muslce biopsies of affected patients to controls, a patient after recovery to themselves during the the disease phase, and compared patients with additional EARS2 mutations to patients without pathogenic EARS2 mutations.

  Study EGAS00001004647

• Mapping_genetic_variants_underlying_gene_regulation_in_inflammed_intestinal_cell_types_to_identify_novel_IBD_drug_targets

  Biopsies from the terminal ileum and rectum of individuals with Crohn's disease are digested on ice to single cells and processed for single-cell RNA-sequencing (10X Genomics and Illumina) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001003770

• Whole-genome bisulfite sequencing analysis of low-grade astrocytomas in the ICGC PedBrain Tumor Project

  Pilocytic Astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well-studied, data of the complete methylome, tumor cell composition and immune infiltration are scarce. We generated whole genome bisulfite sequence data (WGBS) of nine PAs to find evidence for a link of focal methylation differences and differential gene expression to immune infiltration.

  Study EGAS00001004019

• Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

  Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms. We used a multi-omics approach to uncover the molecular factors underlying this heterogeneity and derive a potential disease classification. Transcriptomic analysis of 84 primary PNEN specimens, drawn from two cohorts (n = 36 and 48), identified four subgroups with distinct molecular profiles. Whole-exome sequencing revealed subgroup-enriched mutational differences.

  Study EGAS00001005024

• Brain transcriptome of hereditary cerebral haemorrhage with amyloidosis–Dutch type (HCHWA-D)

  HCHWA-D is an early onset hereditary form of Cerebral Amyloid Angiopathy (CAA) caused by a point mutation resulting in an amino acid change (NP_000475.1:p.Glu693Gln) in the Amyloid Precursor Protein (APP). Post-mortem brain tissue (9 patients and 9 age-related controls; frontal and occipital cortex) was used for next generation sequencing of RNA (RNA-Seq with ribosomal RNA depletion).

  Study EGAS00001002730

• Whole-exome sequencing of Fanconi anemia-like inherited bone marrow failure syndrome

  We identified three fibroblast cultures derived from aplastic anemia patients in the Japanese Cancer Research Resources Bank (JCRB) Cell Bank that showed high levels of sister chromatid exchanges (SCEs) in PHA-stimulated lymphoblasts. To elucidate the genetic basis of the high SCE, we carried out whole exome sequencing of these samples. Subsequently, germline variants were analysed for these patients.

  Study EGAS00001003809

• Whole-exome sequencing of intravascular large B-Cell lymphoma

  Intravascular large B-cell lymphoma (IVLBCL) is a unique form of diffuse large B-cell lymphoma (DLBCL) characterized by extranodal cell growth especially in small vessels without systemic lymphadenopathy. The limitation in obtaining sufficient tumor materials hampers understanding the molecular pathogenesis of IVLBCL. We performed whole-exome sequencing of IVLBCL using plasma-derived cell-free DNA (cfDNA) and patient-derived xenograft (PDX) samples.

  Study EGAS00001003970

• Expression-Based Subtypes Define Pathologic Response to Neoadjuvant Immune-Checkpoint Inhibitors in Muscle-Invasive Bladder Cancer

  Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.

  Study EGAS00001005549

• Transcriptional changes in GBM through therapy

  Primary glioblastoma (GBM) tumours recur following therapy, owing to treatment resistance mechanisms in unresectable cells. We have sequenced RNA from paired primary and locally recurrent GBM tumours to begin characterising therapy resistant cells and thereby infer the mechanisms by which they evaded treatment. Exome sequencing data from these samples were included in the first data release from the Glioma Longitudinal AnalySiS (GLASS) consortium

  Study EGAS00001003790

• Application of Hi-C sequencing to detect structural variants in B-cell acute lymphoblastic leukemia

  Large structural variants are easily detected by Hi-C sequencing as strong, distant signals on a Hi-C contact map. Translocations are frequently evident in B-ALL and accurate identification of these translocations can guide clinical treatment options. Here were apply shallow Hi-C sequencing as an unbiased, cost-effective approach to identify translocations among B-ALL patients.

  Study EGAS00001005605

• IVF Whole genome prediction

  Preimplantation Genetic Testing (PGT) of in vitro fertilized (IVF) embryos has been proposed as a method to reduce transmission of common disease, although comprehensive genetic assessment remains unavailable. Here we use a combination of molecular and statistical techniques to reliably and accurately infer inherited genome sequence in 110 embryos. We combine polygenic risk scores (PRS) and rare variation to model susceptibility across 12 common conditions.

  Study EGAS00001005619

• Cylindromas_sun_protected_and_exposed

  The project aims to look at mutational signatures in a rare inherited skin tumour syndrome called CYLD cutaneous syndrome. These patients develop multiple skin tumours that are seen at sun exposed and sun protected sites. We plan to carry out WGS on carefully curated tumours from such patients. We then plan to analyse this data for mutational signatures, comparing this between sun exposed and sun protected sites.

  Study EGAS00001002521

• ANGIOPREDICT - an FP7-funded project enabling personalised medicine for patients with metastatic colorectal cancer.

  In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers will work together with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to Avastin® combination therapy. Diagnostic tests using these biomarkers will also be developed to provide clinicians with the means to predict patient treatment responses in the future.

  Study EGAS00001005423

• Exome sequencing of paired primary tumor and metastatic breast cancer

  Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of a prospective documentation of metastatic subtyping. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting its transferability to clinical use.

  Study EGAS00001004578

• Molecular landscape of blastic plasmacytoid dendritic cell neoplasm

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow and lymph nodes and sequentially other organ systems. We applied paired WES/RNA-seq combined with genome-wide copy-number analysis to characterize 47 BPDCN patients regarding mutational drivers, cytogenetic aberrations and gene-expression profiles.

  Study EGAS00001006166

• NIHR BioResource Common Disease Patients 2016

  NIHR BioResource Common Disease Patients 2016. The dataset includes 13489 samples from blood donors, they were not screened for any particular disease, and therefore they are representative of the general population. Genomic data includes 845487 snps collected using the UK BioBank V1 Affymetrix array. Phenotypic data includes gender, age, ethnicity and disease. According to our internal quality check there are 81 duplicates in this dataset.

  Study EGAS00001004870

• Single-cell RNA sequencing on single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients.

  Single-cell RNA sequencing on single CD45+ immune cells isolated from peripheral blood, lymphnode, ascites, tumour and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional properties of these individual cells, were used to delineate the molecular subtypes, lineage, and functional properties of each cell group

  Study EGAS00001003449

• Gremlin 1 + fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues

  Although cross-species transcriptional analysis has been generated for DCs37, transcriptomic conservation between mouse and human FRCs at single-cell resolution has been unclear. To test whether GREM1+ FRCs might also play a role in DC homeostasis in humans, we performed scRNA-seq of CD45–PDPN+ stromal cells, as well as CD45+CD11c+ immune cells from healthy human LNs of three donors.

  Study EGAS00001006211

• RNA-seq following miR-130a overexpression (OE) in human CD34+cord blood cells

  We performed RNA-seq on CD34+ human cord blood (CB) cells transduced with Control or miR-130a OE lentiviruses to identify differentially expressed genes. Sorted CD34+ cells from 3 independent cord blood pools were transduced with lentiviruses containing mOrange (mO) reporter gene. mO+ cells were sorted 3 days post-transduction and RNA was harvested for library preparation and sequencing.

  Study EGAS00001005868

• Extensive patient-to-patient single nuclei transcriptome heterogeneity in pheochromocytomas and paragangliomas

  Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors of varied genetic makeup, associated with high cardiovascular morbidity and a variable risk of malignancy. We focused on PCPG tumors with germline SDHB and RET mutations, representing distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) on tissue samples from 11 patients.

  Study EGAS00001006230

• Genetic regulation of gene expression in human brain cell types

  We leveraged single nuclei RNA-seq from 192 human brain samples to map cis-eQTLs in 8 brain cell types. We found extensive cell-type specific genetic effect on gene expression and integrated our results with GWAS to identify putative novel risk genes for brain disorders and the cell types in which the disease mechanisms are likely active.

  Study EGAS00001006345

• Human pan-genome analysis

  The reference human genome is still incomplete, and several non-reference sequences have derived from diverse populations. With the available of whole genome sequencing data from multiple individuals, we could construct the pan-genome sequence. Here we provide high quality genome sequencing (~30x coverage) from 185 Han Chinese individuals. All samples were sequenced using Illumina HiSeq X10 sequencer and paired-end 150-bp reads were produced.

  Study EGAS00001003657

• SDH_deficient_renal_tumours___WGS_

  Succinate dehydrogenase (SDH) deficient renal cancers are a rare and understudied subtype of renal cancer. As such they represent an unmet need in kidney cancer research. Here, we seek to describe the genomics and transcriptomics of SDH deficient renal cancers by sequencing five such tumours. We document their mutational burden, define driver mutations, demonstrate typical patterns of structural variants, and estimate the cell of origin and cellular composition.

  Study EGAS00001004102

• Clonal architecture and genomic features of smoking versus non-smoking oncogene-driven East-Asian non-small cell lung cancer

  Unlike smoking-related non-small cell lung cancers (NSCLC), oncogene-driven tumors are characterized by low mutational burdens and complex genomic landscapes. However, the clonal architecture and genomic landscape of the oncogene-driven tumors in smokers remains unknown. Here, we investigate the impact of tobacco smoking on the genomic and transcriptomic alterations in the context of oncogene-driven NSCLC.

  Study EGAS00001006942

• Identification of Long Non-coding RNA Biomarker of Human Lupus Nephritis Disease Activity

  Total RNA sequencing was performed on whole blood samples from 74 Lupus nephritis (LN) patients and 20 healthy controls. Differential expression analysis and weighted gene co-expression network analysis were performed to characterise expression changes of long non-coding RNAs (lncRNAs) in LN and identify lncRNAs with a key role in disease activity that could be used as potential blood-based biomarkers.

  Study EGAS00001007117

• Age-specific nasal epithelial responses to SARS-CoV-2 infection : GEX

  In this study, we investigate differences in the cellular landscape and functionality of ex vivo cultured nasal epithelial cells in response to SARS-CoV-2 infection across different age groups: paediatric (<12y), adult (30-50y), and older adults (>70y). We unravel, that while ciliated cells serve as primary sites for viral replication consistently across all age groups, a distinctive goblet inflammatory subtype emerges in infected paediatric cultures, characterized by heightened expression of interferon-stimulated genes and incomplete viral replication. Conversely, older adult cultures infected with SARS-CoV-2 exhibit a proportional surge in basaloid-like cells, which not only facilitate viral dissemination but also demonstrate associations with altered epithelial repair pathways.

  Dataset EGAD00001015345

• HV31 - Read identifier list for local CCS, CLR, ONT and MGI reads

  This file contains read identifiers for local CCS, CLR, ONT and MGI reads for each of the eight selected genomic regions (HLA, KIR, IGH, IGK, IGL, TRA, TRD, andTRG). We extracted these reads by aligning whole-genome sequencing data to a draft whole-genome de novo assembly, and selecting reads that map to contigs representing each region. These reads were involved in the polishing and validation of the HV31 assembly. Please refer to the relevant manuscript (https://doi.org/10.1101/2021.02.03.429586) for additional details. Read identifiers are stored in JSON format. Along with the full FASTQ files, this file enables convenient re-analysis of the HV31 sequencing data in the eight selected regions.

  Dataset EGAD00001007761

• RNAseq files for Klco RPAML

  RNAseq files for Klco RPAML study titled "Genomics of pediatric myeloid neoplasms"

  Dataset EGAD00001008407

• ATAC-seq dataset of Single cell RNA sequencing reveals induced bifurcated differentiation after RUNX1::RUNX1T1 depletion in patient-derived leukemic blasts

  In this study, we demonstrate that primary AML cells harboring the chromosomal translocation t(8;21) are critically dependent on the corresponding fusion gene, RUNX1::RUNX1T1, to suppress differentiation and maintain stemness. Silencing RUNX1::RUNX1T1 expression using siRNA-loaded lipid nanoparticles induces significant changes in chromatin accessibility, redirecting the leukemia-associated transcriptional network towards a myeloid differentiation program. Single-cell analyses reveal that this transcriptional reprogramming is associated with the depletion of immature stem and progenitor-like cell populations, accompanied by an expansion of granulocytic and eosinophilic/mast cell-like populations with impaired self-renewal capacity.

  Dataset EGAD00001015509

• scRNA-seq dataset of Single cell RNA sequencing reveals induced bifurcated differentiation after RUNX1::RUNX1T1 depletion in patient-derived leukemic blasts

  In this study, we demonstrate that primary AML cells harboring the chromosomal translocation t(8;21) are critically dependent on the corresponding fusion gene, RUNX1::RUNX1T1, to suppress differentiation and maintain stemness. Silencing RUNX1::RUNX1T1 expression using siRNA-loaded lipid nanoparticles induces significant changes in chromatin accessibility, redirecting the leukemia-associated transcriptional network towards a myeloid differentiation program. Single-cell analyses reveal that this transcriptional reprogramming is associated with the depletion of immature stem and progenitor-like cell populations, accompanied by an expansion of granulocytic and eosinophilic/mast cell-like populations with impaired self-renewal capacity.

  Dataset EGAD00001015510

• Dataset for Sarcoma-WES linked from study EGAS00001004813

  Sequencing data of 144 sarcoma tumor and control runs, which were uploaded to EGAS00001004813. The sequencing was always paired.

  Dataset EGAD00001010258

• G-SAM: Transcriptional Evolution of Glioblastomas Treated With Standard of Care

  Collection of mostly matching primary and recurrent glioblastoma RNA-seq sample pairs, also matching with an earlier DNA sequencing study

  Dataset EGAD00001007860

• WGS files for Klco RPAML

  WGS files for Klco RPAML study titled "Genomics of pediatric myeloid neoplasms"

  Dataset EGAD00001008413

• Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens

  In this study we performed whole genome sequencing on matched tumor-normal CD138+ bone marrow mononuclear cells from 60 patients with newly diagnosed multiple myeloma treated with daratumumab, carfilzomib, lenalidomide, and dexamethasone (NCT03290950-MANHATTAN trial). In addition, we performed 5’-single-cell RNA-sequencing (10X Genomics) coupled with V(D)J sequencing and capture of the surface protein markers (TotalSeq-C, Biolegend) of the CD138- bone marrow mononuclear cells to interrogate the composition of the immune microenvironment at baseline and after eight cycles of induction therapy in 22 patients with newly diagnosed multiple myeloma. Samples were multiplexed using hashtag oligo.

  Dataset EGAD00001011132

• The G2 gene expression signature and MYC overexpression are independent poor prognostic factors in childhood high-grade osteosarcoma

  Key objective Are the prognostic transcriptomic G1/G2 gene expression signature, MYC overexpression, and MYC amplification replicable stratifying biomarkers for future clinical trials in high-grade osteosarcoma? Knowledge gathered In an unselected cohort, the G2 gene expression signature and MYC overexpression, but not MYC amplification, were independently associated with poor event-free and overall survival. Relevance Transcriptomic biomarkers may serve as stratifying factors that guide the management of patients with high-grade osteosarcoma. Current data underlines the importance of prospective validation of the G1/G2 signature and MYC overexpression in an international, multicenter, study.

  Dataset EGAD00001015503

• ICARUS-LUNG01 dataset

  A total of 46 frozen tumor biopsies underwent WES analysis, while 41 blood samples were used as germline controls.Tumor samples qualified for whole exome sequencing (WES) if they contained ≥10% tumor cells. For bulk RNA-seq, 20 paired baseline and on-treatment frozen tumor biopsies were analyzed. Tumor samples qualified if they contained ≥30% tumor cells. For GeoMx spatial transcriptomic study we used 7 patients from the ICARUS LUNG01 trial focusing on tumour and immune cell compartments. We selected 7 paired baseline and on-treatment patient samples for analysis. We selected up to 4 regions of interest (ROI) per sample tissue. We identified tumour and immune cell areas of illumination (AOI) using CK and CD45 antibodies respectively

  Dataset EGAD50000001014

• Microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma

  Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.

  Study EGAS00001006052

• A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer

  Brief SummaryThis randomized phase II trial studies the side effects of durvalumab and tremelimumab to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal (CRC) or non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.Detailed DescriptionPRIMARY OBJECTIVES:I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort)SECONDARY OBJECTIVES:I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort)OUTLINE: Patients are assigned to 1 of 2 cohorts. NOTE: This Study is only for Cohort 2. Please see phs003295 for Cohort 1COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms.ARM A: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.ARM C: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.COHORT 2: Patients with CRC are randomized to 1 of 2 arms.ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.After completion of study treatment, patients are followed for up to 12 weeks.Official TitleA Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC Conditions Metastatic Colorectal CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Colorectal Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Stage IVB Colorectal Cancer AJCC v7 Intervention/Treatment Biological: DurvalumabRadiation: Radiation TherapyBiological: Tremelimumab Other Study ID Numbers NCI-2016-01325NCI-2016-01325 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))17-71910021 ( Other Identifier ) (OTHER: Dana-Farber - Harvard Cancer Center LAO)10021 ( Other Identifier ) (OTHER: CTEP) Molecular Technologies/AssaysIHCmIFOlinkCyTOFRNAseqWES

  Study phs003294