View clinical trials related to Microsatellite Instability.
Filter by:Over the last ten years, the discovery of the mechanisms by which tumours escape the control of the immune system, and in particular the T lymphocyte response, has led to the emergence of new therapeutic strategies against cancer, such as the use of "immune checkpoint inhibitors" (ICI). The immune system plays a crucial role in controlling tumour proliferation, and involves several players. Schematically, after recognition of the MHC-peptide complex by the TCR, the T lymphocyte response is modulated by several activating or inhibiting co-stimulatory signals (or "checkpoints"). The balance of these different signals determines whether the T lymphocyte (LT) is activated, resulting in the destruction of the target cell, or whether the T lymphocyte is inhibited (anergy), inducing immune tolerance. By hijacking this system through the expression of inhibitory checkpoints on its surface, the tumour cell is able to evade the effector immune response (1). Monoclonal antibodies (mAbs) directed against inhibitory co-stimulatory molecules such as Programmed-cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) or their ligand Programmed-cell death ligand 1 (PD-L1) have been developed to restore effective anti-tumour immunity. These ICIs have led to a major improvement in the prognosis of certain cancers, notably melanoma and non-small cell lung cancer. However, the efficacy of ICIs varies from one cancer to another. In addition to the expression of PDL1 by the tumour and/or immune cells, and the mutational load, one of the primary factors predicting response to immunotherapy mentioned in several studies is microsatellite instability (MSI).
This study is being conducted to evaluate efficacy parameters (disease free survival [DFS] and overall survival [OS]) of atezolizumab and atezolizumab in combination with tiragolumab in TMB-H or MSI-H as adjuvant treatment after standard radical intended treatment in participants with intermediate-high risk of recurrence.
The distribution rate of microsatellite instability-high (MSI-H) was significantly higher in early-onset colorectal cancer, and early-onset colorectal cancer has a specific mutational profile and relatively high programmed cell death ligand 1(PD-L1) expression, which may be used to guide personalized treatment to better control the disease.
This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled brain metastasis. The study will have three phases, Phase 1, Phase 2a and Phase 2b.
This is a Phase 1, open-label, dose escalation and expansion study of MT-8421 (an Engineered Toxin Body (ETB)) as monotherapy and in combination with nivolumab in patients with selected advanced solid cancer types. MT-8421 is an investigational drug that specifically targets and depletes cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) expressing cells in an effort to directly dismantle the tumor microenvironment for the treatment of patients with advanced solid tumors.
This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RO7589831 monotherapy in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advanced solid tumors. RO7589831 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, RO7589831 may be able to block the growth of these types of cancer.
This study will evaluate the safety, and tolerability of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with dMMR/MSI-H.
The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in participants with select solid tumors.
The main purpose of the study is to evaluate the safety and tolerability of HRO761 and identify the recommended dose(s), i.e., the optimal safe and active dose of HRO761 alone or in combination with tislelizumab or irinotecan that can be given to patients who have cancers with specific molecular alterations called MSIhi (Microsatellite Instability-high) or dMMR (Mismatch Repair Deficient) that might work best to treat these specific cancer types and to understand how well HRO761 is able to treat those cancers.
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