View clinical trials related to MSI-H Colorectal Cancer.
Filter by:Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Microsatellite instability or mismatch repair deficiency occurs in 20% of CRC, and is predominantly found in non-metastatic tumors. The success of the CheckMate 142 and KEYNOTE-177 clinical trials has shifted the treatment paradigm of the MSI/dMMR CRC, which has led to the adoption of immune checkpoint inhibitors (ICI) by international treatment standards. However, despite the encouraging effects of ICI, up to 30% of patients are resistant to treatment and exhibit rapid disease progression shortly after starting ICI. On the other hand, around 30% of patients treated with ICI demonstrate prolonged responses to the treatment with a duration of response of over 40 months. Furthermore, for ~10% of patients, treatment with ICI results in pseudo-progression - a phenomenon of a short-term increase followed by the decrease of the tumor volume. Currently, the mechanisms and biomarkers associated with the response or resistance to ICI in MSI-positive CRC are largely unknown. Select studies suggest that BRAF mutations (specifically, BRAF p.V600E) might negatively affect the patients' progression-free survival following ICI, however, these data are premature. The primary hypothesis is that the clonal heterogeneity and the evolution of MSI status of MSI-positive CRC will play a role in the development of ICI treatment resistance. The primary objective of the study is to investigate the dynamics of MSI status in serial liquid biopsy samples from patients with MSI-positive tumors receiving ICI.
This study is an open-label, multi-arm, parallel cohort, dose validation and expansion design. The study is modular in design, allowing evaluation of the safety, efficacy and pharmacokinetics (PK) of NUC-3373 in combination with other agents for the treatment of patients with different tumour types. Each module is designed to evaluate a different NUC-3373 combination and consists of a dose-validation phase (Phase Ib) and a dose-expansion phase (Phase II). Phase Ib of each module will determine the safety and tolerability of the combinations for further clinical evaluation in Phase II. Approximately 6-20 evaluable patients will be enrolled in the Phase Ib stage of each module to determine safety, tolerability, and preliminary efficacy of NUC-3373 in combination with other agents. Each module will then move into Phase II to enable a further assessment of safety and efficacy in approximately 20-40 patients. Module 1 will assess NUC-3373 + leucovorin (LV) in combination with pembrolizumab for the treatment of patients with advanced/metastatic solid tumours who have progressed on ≤2 prior therapies for metastatic disease, that may have included 1 prior immunotherapy-containing regimen (either monotherapy or in combination with chemotherapy) or who have not progressed but where addition of NUC-3373 + LV to standard pembrolizumab monotherapy may be appropriate (e.g., patients who could not tolerate post- immuno-oncology (IO) standard of care therapy). Module 2 will assess NUC-3373 + LV in combination with docetaxel for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease. The opening of each module will be at the discretion of the Sponsor. Further modules may be added as non-clinical and clinical data become available to support additional NUC-3373 combinations and tumour types.
This is a monocentric, prospective, pilot study that will enrol 435 subjects with solid tumours that are treated with immune checkpoint inhibitor(s) (ICI) alone or in combination with chemotherapy or targeted therapy. For enrolled subjects, clinical and laboratory evaluations will be performed and reported at different time points: - Early (4-6 weeks after treatment start) - Midtime (8-11 weeks after treatment start) - Late (13-18 weeks after treatment start) - At the occurrence of immune-related adverse events (irAEs), clinical and laboratory evaluation will be performed at two principal time points: - For the 1st time of any grade 1 or 2 irAE if the subject developed it. - For the 1st time of any grade 3 or 4 irAE if the subject developed it.
This is an open-label, parallel group, non-randomized, multicenter phase II study to evaluate the efficacy of spartalizumab (cohorts 1 and 2) and tislelizumab (cohort 3) in monotherapy in patients with PD1-high-expressing tumors.
NIPISAFE is open-label, phase II study to identify a combination scheme of nivolumab and ipilimumab with a high level of clinical activity, but with a lower toxicity in MSI/dMMR metastatic colorectal cancer patients.