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

NCT06414304 | Completed

• 2 other identifiers: BLOOMSI22-75-10154
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Colorectal Cancer; Colorectal Cancer Metastatic; MSI-H Colorectal Cancer; dMMR Colorectal Cancer; Cancer; Colon Adenocarcinoma

Keywords

MSI; dMMR; Microsatellite instability; Next-generation sequencing; Immunotherapy; Immune checkpoint inhibitors; Colorectal cancer

Outcome Measures

Primary Outcomes (1)

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

  Concordance will be calculated using Cohen's Kappa (κ)

  Through study completion, an average of 3 years

Secondary Outcomes (2)

• Concordance of MSI in tumor tissue and liquid biopsy (ctDNA)

  Through study completion, an average of 3 years

• Qualitative and quantitative status of MSI in serial liquid biopsy (ctDNA) samples

  Through study completion, an average of 3 years

Other Outcomes (2)

• Correlation of biomarkers with the treatment outcomes

  Through study completion, an average of 3 years

• Evaluation of the ctDNA dynamics in the course of ICI in serial plasma samples

  Through study completion, an average of 3 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with histologically confirmed colorectal cancer with microsatellite instability (MSI) or mismatch repair deficiency (dMMR)

You may qualify if:

• Male/female participants must be at least 18 years of age on the day of signing informed consent and have a histologically confirmed diagnosis of colorectal cancer.
• Verified MSI/dMMR positivity as measured by 5-loci PCR or 4-antibody IHC.
• Have provided an archival tumor tissue sample obtained prior to the start of treatment with immune checkpoint inhibitor(s). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
• Patient has to be able to provide serial blood samples during the course of treatment, as well as on every follow-up tumor scan.
• The participant (or legally acceptable representative if applicable) provides written informed consent to participate in the trial.
• Have measurable disease based on RECIST 1.1.
• Have adequate organ function.

You may not qualify if:

• Prior treatment with immune checkpoint inhibitors.
• For female participants: pregnancy or planned pregnancy.
• The unavailability of the tumor or serial liquid biopsy samples.

Sponsors & Collaborators

• OncoAtlas LLC: lead
• N.N. Blokhin National Medical Research Center of Oncology: collaborator
• Moscow MultidisciplinaryClinical Center Kommunarka: collaborator

Study Sites (2)

N.N.Blokhin National Medical Research Center of Oncology

Moscow, 115478, Russia

Location

State Budgetary Institution of Healthcare of the City of Moscow "Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Health of the City of Moscow

Moscow, 142770, Russia

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms; Colonic Neoplasms; Microsatellite Instability

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Maxim Ivanov, PhD

  OncoAtlas LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 16, 2024
• Study Start: June 1, 2022
• Primary Completion: September 1, 2024
• Study Completion: March 1, 2025
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

RU (2)