Dynamics of MSI and Genomic Profile of Colorectal Cancer In the Course of Immune Checkpoint Inhibitor Therapy - Trial NCT06414304

Timeline & Enrollment

Primary Outcome

Concordance of NGS and routine methods (PCR, IHC) for MSI analysis

Summary

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.

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