Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Toripalimab Plus Bevacizumab and Chemotherapy as Neoadjuvant Therapy in Advanced MSI-H or dMMR Colorectal Cancer

ABSTRACT: This is a trial investigating the efficacy and safety of Toripalimab combined with bevacizumab and chemotherapy as neoadjuvant therapy in patients with advanced microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR) colorectal cancer.

DISEASE(S): Colorectal Carcinoma,Colorectal Neoplasms

PROVIDER: 2385325 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer

Project description:Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% of all CRC patients, and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in "N Engl J Med" showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response. In theory, anti-PD-L1 drugs should have fewer immune side-effects than anti-PD-1 drugs. However, there are no reports of anti-PD-L1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to investigate the efficacy and safety of anti-PD-L1 monoclonal antibody (Envafolimab) as neoadjuvant immuntherapy for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.

| 2729957 | ecrin-mdr-crc

Dickkopf 1 Impairs Sensitivity to PD-1 Blockade through CD8+ T Cell Inactivation in dMMR/MSI Colorectal Cancer

Project description:Dickkopf 1 (DKK1) could promote tumor progression by suppressing immunity. Therefore, we investigated whether DKK1 influence prognosis and sensitivity to PD-1 blockade in colorectal cancers (CRCs) with defective DNA mismatch repair genes (dMMR) or microsatellite instability (MSI). We found that elevated DKK1 expression was associated with recurrence and dismissed CD8+ T cell infiltrations, and patients with high serum DKK1 had poor anti-PD-1 response. RNA interference or neutralization of DKK1 in CRCs enhanced CD8+ T cell cytotoxicity, and down-regulation of T-bet and E2F1 following GSK3β activation was detected in DKK1-treated CD8+ T cells. In organoid-lymphocyte co-culture model, apoptosis proportions were elevated after individual neutralization of both PD-1 and DKK1, and the combined neutralization resulted in further increases. In conclusion, DKK1 suppresses tumor immunity in dMMR/MSI CRCs by inactivating CD8+ T cells through GSK3β/E2F1/T-bet axis. DKK1 neutralization may improve the sensitivity to PD-1 blockade in dMMR/MSI CRCs.

2021-04-07 | GSE149206 | GEO

Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer

Project description:Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher proportion in right colon cancer. Previous studies have found that colon cancer patients with dMMR/MSI-H cannot benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and the prognosis is significantly worse than that of mismatch repair-proficient (pMMR)/microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in 《N Engl J Med》 showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy. Anti-PD-1 neoadjuvant therapy has proven to be safe and feasible in lung cancer, bladder cancer and malignant melanoma, and can achieve more than 40% of major pathological response. However, there are no reports of anti-PD-1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to find the best multidisciplinary treatment for resectable colorectal cancer patient with the dMMR/MSI-H phenotype and to explore whether cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could further improve efficacy.

| 2303741 | ecrin-mdr-crc

The mCRC Patients With pMMR/MSS or dMMR/MSI-H Status Received Palliative Chemotherapy Efficacy and Survival

Project description:Deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) accounts for 4-5% in metastatic colorectal cancer (mCRC). The efficacy and survival of patients with dMMR/MSI-H status received palliative chemotherapy have not clear yet. In this study, the investigators observed the efficacy and survival of dMMR/MSI-H status mCRC patients received palliative first-line chemotherapy.

| 2346468 | ecrin-mdr-crc

IBI310 in Combination With Sintilimab in Patients With DNA Mismatch Repair Deficient (dMMR)/Microsatellite Instability High (MSI-H) Locally-advanced or Metastatic Colorectal Cancer

Project description:The main purpose of this study is to assess the efficacy and safety of IBI310 in combination with sintilimab in patients with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) locally advance or metastatic colorectal cancer.

| 2329228 | ecrin-mdr-crc

A Study of HX008 Compared to Chemotherapy in the First-Line Treatment of Subjects With MSI-H/dMMR Metastatic Colorectal Cancer

Project description:The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), achieved by HX008 or Investigator’s Choice Chemotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC).

| 2559 | ecrin-mdr-crc

Genome-wide analysis of miRNA levels in colon cancer

Project description:Analysis of miRNA levels found in tissue obtained from proficient mismatch repair (pMMR) TNM stage 2|3|4 colon tumor, deficient MMR (dMMR) colon tumor, and normal colon. miRNA levels obtained from macrodissected colon tumors with > 70% H&E staining were compared with normal colon tissue. Additional comparisons based on mismatch repair status identified by loss of hMLH1 protein and microsattelite instability assay and TNM stage were carried out. This submission provides access to the data discussed in our paper. The supplementary file 'GSE18392_non-normalized_data.txt' file contains non-normalized data for Samples GSM458618-GSM458762.

2010-03-18 | E-GEOD-18392 | biostudies-arrayexpress

scRNAseq of orthotopic mismatch repair deficient (dMMR) or chromosomally instable (CIN) colorectal cancer

Project description:Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8+ T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8+ T cells into dMMR CRCs strictly depends on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be upregulated by common chemotherapies in all CRCs, indicating that facilitating CD8+ T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs where local priming can be maximized even in neoantigen-poor CRCs.

2021-07-19 | GSE178706 | GEO

A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator’s Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)

Project description:The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS), achieved by nivolumab in combination with ipilimumab or by nivolumab monotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC). This study will also compare nivolumab plus ipilimumab combination vs chemotherapy for treatment of MSI-H/dMMR mCRC participants.

| 2310012 | ecrin-mdr-crc