Prospective National Cohort Evaluating Predictive Biomarkers of Resistance to Immunotherapy in Patients With MSI/dMMR Metastatic Colorectal Cancer (CORESIM)

Federation Francophone de Cancerologie Digestive

Status: Enrolling

Conditions: Microsatellite Instability-High Colorectal Cancer; Colorectal Cancer Metastatic

Study type: Observational

Funder types: Other

Identifiers

NCT06353854

FFCD 2112-CORESIM

Details and patient eligibility

About

The Keynote 117 phase III trial demonstrated the superiority of pembrolizumab (anti-PD1 monoclonal antibody) versus chemotherapy +/- targeted therapy in first-line treatment of dMMR/MSI metastatic colorectal cancer (mCRC). However, primary resistance to pembrolizumab was observed in approximately 20-30% of patients treated in the Keynote 177 study. Therefore, the identification of biomarkers predictive of resistance to immunotherapy for dMMR/MSI mCRC is necessary to better select patients who benefit the most from immunotherapy, and those for whom other therapeutic approaches should be favored.

Full description

The primary endpoint is the identification of predictive factors of resistance to pembrolizumab in first-line treatment of MSI and/or dMMR metastatic colorectal cancer

CORESIM is a retrospective and prospective multicenter national French cohort. National recruitment will be carried out in all French centers, including the FFCD, AGEO, GERCOR, and UNICANCER, representing more than 150 centers and most French sites, public and private hospitals.

In France, pembrolizumab for first-line treatment of patients with MSI mCRC was accessible via its compassionate use in February 2021, then its reimbursement was effective in June 2023 Patients treated with pembrolizumab will be included prospectively on the start date of the study, i.e. on February 2024; patients treated since February 2021 via compassionate use of pembrolizumab will be included retrospectively A total of 600 patients are expected. The theoretical duration of inclusion is set at 2 years. All patients will be followed up for 3 years.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients over 18 years old
• Histologically confirmed colorectal adenocarcinoma with unresectable metastasis(s) receiving immunotherapy as first-line treatment with pembrolizumab
• Tumor with microsatellite instability determined by immunohistochemistry (loss of expression of MLH1, MSH2, MSH6 and/or PMS2) and/or by molecular biology (MSI-H on microsatellite analysis from tumor DNA according to practice routine of the center)

Exclusion criteria

• Patients with another concomitant cancer at the time of diagnosis requiring systemic treatment or impacting prognosis according to the medical team.
• Previous treatment with anti-PD1 or anti-PDL1.
• Previous treatment with chemotherapy +/- targeted therapy for MSI/dMMR metastatic colorectal cancer.
• Contraindication due to psychological or social reasons that may hinder follow-up (cognitive deficit, psychological disorders incompatible with obtaining non-opposition or consent; inability to be followed in the same center throughout the follow-up period for geographical reasons).
• Pregnant women
• persons under court protection or under protective supervision (guardianship or curatorship)
• Opposition to participation in the study.

Trial design

600 participants in 2 patient groups

Retrospective group

Description:

Registration of patients treated with pembrolizumab since February 2021. Collection of tumour sample archives will be associated

Prospective group

Description:

Recruitment of metastatic colorectal cancer patients with microsatellite instability prior to the first administration of pembrolizumab immunotherapy. Blood and tumour sampling will be combined.