View clinical trials related to Microsatellite Stable.
Filter by:This is aPhase II Study of Leronlimab (PRO 140) in combination with Regorafenib in Patients with CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)
This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors
Explore the efficacy of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer patients; To evaluate the safety and tolerability of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer; To evaluate the radiosensitization effects of Tslelizumab and irinotecan;
About 85% of cases of non-metastatic colorectal cancer (CRC) are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR); which are also called CRC with microsatellite stability (MSS). Other CRC, i.e. 15%, are "microsatellite unstable" (MSI) with deficient DNA Mismatch-Repair system (dMMR). These latter are characterised by generation of many neo-antigens, which result in a high anti-tumour immune response and a high peri- and/or intra-tumour lymphocyte infiltration (TIL). Investigators recently showed, with a prospectively validated immune score, that 14% of localised MSS/pMMR CRC are also highly infiltrated by CD3+ lymphocytes. This same immune score has made it possible to measure high lymphocyte infiltration in hepatic metastases, in particular, in patients treated with XELOX/FOLFOX. Pembrolizumab, an anti-PD1 monoclonal antibody (programmed death-1) is an immune checkpoint inhibitor (ICI) of PD1/PD-L1 axis, recently approved in many cancers. Anti-PD1 antibodies have recently been reported as being very effective in patients with dMMR metastatic CRC (mCRC). In the study by Le DT et al. pMMR mCRC did not seem to benefit from anti-PD1 antibodies. However, it is possible that 20% of pMMR mCRC with a high CD3+ infiltrate in the tumour may be a subgroup of pMMR mCRC sensitive to ICI, as is the case for dMMR mCRC. Lastly, immunogenic cell death induced by chemotherapy, such as oxaliplatin, can increase the efficacy of ICI. The prognostic value of lymphocyte infiltrate has been demonstrated in CRC by several teams. However, no validated test is used in routine clinical practice. Previously, investigators described an automated and reproducible method for analysis of TIL and investigators validated it for clinical use. Automated tests evaluating TIL are performed on virtual slides and have showed that, out of 1,220 tumours tested, 20% were highly infiltrated by CD3+ T cells. Patients presenting with a pMMR CRC with a high immune infiltrate had a better progression-free survival (HR=0.70; p=0.02). An immunoscore® described by Galon et al. has also a high prognostic value in CRC and is based on CD3+ and CD8+ T cells infiltration in the center and periphery of the tumour. Finally, approximately 14% of tumours with a high immune infiltrate have been found in patients with metastatic CRC. Investigators formulated the hypothesis that patients with a pMMR CRC with a high immune infiltrate can be sensitive to ICI . Therefore, blocks of resected primary tumour will be collected and analysed prospectively. For each patient, slides containing tumour tissue and adjacent non-tumour tissue will be analysed using two techniques : immunoscore® and TuLIS score.It consist in Immunohistochemistry with CD3 and CD8 staining. Slides will be scanned and analysed by image analysis as previously described . Tumours will then be classified as having a "high" or "low" immune response according to type of lymphocyte infiltrate, which is independent of pre-analytic conditions. Only patients with a high immune response will be eligible for the POCHI trial. Other biomarkers will be analysed like other immune populations or mutational load. If investigators identify an immune score which seems clinically relevant to predict sensitivity to ICI in pMMR mCRC, this will make it possible to plan a randomised phase III trial comparing chemotherapy and anti-angiogenic antibody versus chemotherapy and anti-angiogenic antibody plus pembrolizumab in patients with a pMMR mCRC with a high immune score and/or a hypermutated genotype. Investigators choose PFS at 10 months as primary endpoint in POCHI trial because it is a surrogate marker of OS. Actually median PFS in first-line setting with a doublet plus a biological agent is range from 8 to 11 months in unresectable mCRC, corresponding to a PFS of 50% at 10 months. The alternative clinical hypothesis to obtain 70% of patients alive and without progression at 10 months is ambitious and currently not achieved with current chemotherapies plus a biological agent. Up until now there is no data concerning survivals outcomes of patients with a MSS mCRC with high immune infiltration score.
A phase II clinical study of Sintilimab (IBI308) combined with Bevacizumab, Oxaliplatin and Capecitabine regimen as first-line treatment in patients with RAS-mutant and microsatellite stable metastatic colorectal cancer. A total of 25 patients are planned to be enrolled.
This phase IIa trial studies how well rintatolimod and pembrolizumab works in treating patients with colorectal cancer that does not respond to treatment (refractory), has spread to other places in the body (metastatic), or otherwise cannot be removed by surgery (unresectable). Rintatolimod is an immuno-oncology agent that can stimulate the immune system. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving rintatolimod and pembrolizumab together may work better than standard of care in treating patients with colorectal cancer.
This phase II trial studies the side effects and how well niraparib and panitumumab work in treating patients with colorectal cancer that has spread to other places in the body. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and panitumumab may work better in treating patients with colorectal cancer.
This phase II trial studies the side effects and best dose of capecitabine when given together with pembrolizumab and bevacizumab, and investigates how well they work in treating patients with microsatellite stable colorectal cancer that has spread to nearby tissues or lymph nodes, has spread to other places in the body, or that cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving capecitabine together with pembrolizumab and bevacizumab may work better in treating patients with colorectal cancer.