Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Study of Durvalumab and Tremelimumab After Radiation for Microsatellite Stable Metastatic Colorectal Cancer Progressing on Chemotherapy

ABSTRACT: This study is being done to look at the safety and response to the combination of two investigational drugs, tremelimumab and durvalumab, when given after radiation therapy for patients with microsatellite stable (MSS) metastatic colorectal cancer. Tremelimumab and durvalumab recognize specific proteins on the surface of cancer cells and trigger the immune system to destroy the cancer cells. In order to learn more about certain characteristics of colorectal cancer tumors, this study includes special research tests using samples from diagnostic tumors, fresh tumor samples from an area where the cancer has spread, and blood samples.

DISEASE(S): Colorectal Neoplasms,Colorectal Cancer Metastatic

PROVIDER: 2233185 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial [RNA-Seq]

Project description:While patients with microsatellite instable, metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single arm, phase IB/II MEDITREME trial evaluates safety and efficacy of durvalumab plus tremelimumab in combination with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable mCRC. Safety was primary objective of phase IB and no safety issue was observed. The primary objective of phase II was efficacy in terms of 3-month PFS in MSS patients, which was met with a 3 month PFS of 90.7% [95% CI: 79.2-96%]. For secondary objective, response rate was 64.5%, median PFS was 8.2 months [95% CI: 5.9–8.6] and overall survival was not reached in MSS patients. Higher tumor mutational burden and a lower degree of genomic instability in responder patients. Integrated transcriptomic analysis underlined that high immune signature, and low epithelio-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC.

2023-07-05 | GSE235919 | GEO

First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial [scRNA-Seq]

2023-07-05 | GSE235917 | GEO

Effects of durvalumab alone or combined with tremelimumab on preexisting cells in the tumor microenvironment

Project description:Immune checkpoint blockade with anti–PD-1/L1 or anti–CTLA-4 therapies has shown promising results across multiple cancer types, but the mechanisms within the tumor microenvironment (TME) have not been fully characterized. We used single-cell RNA sequencing to investigate the effects of anti–PD-L1 monoclonal antibody (mAb) durvalumab (D) alone and combined with an anti–CTLA-4 mAb, tremelimumab (T), on distinct subsets of immune cells. Upon treatment with D or D+T, two NSCLC tumors showed elevated IFNγ responses, although they differed in magnitude of response but differed in other areas. Our results highlight that D and D+T in the TME have some consistent effects across tumors but also exhibit tumor-specific effects depending on composition and functional state of immune cells in the TME at time of treatment. This complex tumor-specific interplay of diverse immune subtypes in the TME is critical to better understand patient response to immunotherapy.

2021-09-01 | GSE131933 | GEO

A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

Project description:This was a Phase 1, open-label, nonrandomized, multicenter study of durvalumab and tremelimumab in subjects with advanced cancers who were not eligible for, declined, or failed standard treatment. The primary study objective was to determine the maximum tolerated dose (MTD) and safety profile of the durvalumab and tremelimumab combination. Secondary objectives were to evaluate the pharmacokinetics (PK) and immunogenicity of durvalumab and tremelimumab, and the antitumor activity (tumor response, progression-free survival [PFS], and overall survival [OS]) of the durvalumab and tremelimumab combination. (Note: Collection of PK and immunogenicity samples was removed by amendment; analysis was not done.) Exploratory objectives were to evaluate the biological activity of the durvalumab and tremelimumab combination.

| 2154156 | ecrin-mdr-crc

Durvalumab (MEDI4736) with or without tremelimumab in MSS and MSI colorectal and endometrial tumors

Project description:Primary objectives: To assess the antitumor activity of Durvalumab or Tremelimumab 300 mg single dose followed by Durvalumab in patients with microsatellite instable (MSI) colorectal cancer (CRC) or endometrial cancer (EC) and Tremelimumab 300 mg single dose followed by Durvalumab in refractory microsatellite stable (MSS) CRC and EC as defined by objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Primary endpoints: Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and iRECIST if applicable, in patients with advanced, immune naïve MSS CRC, MSS EC, MSI CRC and MSI EC.

| 2735605 | ecrin-mdr-crc

Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer

Project description:This randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer 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.

| 2224080 | ecrin-mdr-crc

Durvalumab and Tremelimumab in Treating Patients With Microsatellite Stable Metastatic Colorectal Cancer to the Liver

Project description:This pilot clinical trial studies the side effects and how well durvalumab and tremelimumab work in treating patients with microsatellite stable colorectal cancer that has spread to the liver. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.

| 2233000 | ecrin-mdr-crc

Whole Blood RNA Transcript Models Predict Clinical Response in Two Clinical Studies Advanced Melanoma Patients Treated with Tremelimumab

Project description:Background: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. Methods: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset). A central panel of radiologists determined objective response using RECIST criteria. Gene expression for 169 mRNA transcripts was measured using quantitative PCR. A 15-gene pre-treatment response-predictive classifier model was identified. An independent population (N=150) of refractory melanoma patients receiving tremelimumab after chemotherapy enrolled in a worldwide phase II study (validation dataset). The classifier model using the same genes, coefficients and constants for objective response and one-year survival after treatment was applied in the validation dataset. Results: A 15-gene pre-treatment classifier model (containing ADAM17, CDK2, CDKN2A, DDP4, ERBB2, HLA-DRA, ICOS, ITGA4, LARGE, MYC, NAB2, NRAS, RHOC, TGFB1, and TIMP1) achieved an area under the curve (AUC) of 0.86 (p< 0.0001) in the discovery set. This model was validated in the validation set with AUCs of 0.641 (p= 0.049) for objective response and 0.68 for one-year survival (p=0.0002). Conclusions: To our knowledge, this is one of the largest blood-based biomarker studies of a checkpoint inhibitor, tremelimumab, which demonstrates a validated pre-treatment mRNA classifier model that predicts clinical response. The data suggest that the models capture biological signatures representative of genes needed for a robust anti-cancer immune response. They also identify non-responders to tremelimumab significantly prior to radiological evidence of progression.

2017-02-15 | GSE94873 | GEO

nCounter analysis of mRNAs associated with muscle invasive urothelial bladder carcinoma (MIBC) using a Nanostring custom assay

Project description:Gene profiling analysis to evaluate pre- and post-immune checkpoint therapy with tremelimumab (anti-CTLA-4) plus durvalumab (anti-PD-L1) as neoadjuvant treatment prior to radical cystectomy in MICB were analyzed using customized 749- gene Nanostring panel

2022-11-01 | GSE140278 | GEO

Basket Trial for Combination Therapy With Durvalumab (Anti-PDL1) (MEDI4736) and Tremelimumab (Anti-CTLA4) in Patients With Metastatic Solid Tumors

Project description:To determine the efficacy (as measured by overall tumour response rate) of the combination of durvalumab and tremelimumab when given to previously treated patients with solid tumors harboring a high mutational load.

| 2308027 | ecrin-mdr-crc

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data