Clinical trial NCT06353854: Prospective National Cohort Evaluating Predictive Biomarkers of Resistance to Immunotherapy in Patients With MSI/dMMR Metastatic Colorectal Cancer (CORESIM)
Official title: National French Cohort Evaluating Predictive Factors of Resistance to Immunotherapy in Patients With MSI Metastatic Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer Metastatic
Microsatellite Instability-High Colorectal Cancer
Keywords: immunotherapy resistance
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Prospective inclusion of patients receiving first-line immunotherapy with pembrolizumab (as defined in the MA) for unresectable mCRC.

Patients who have received pembrolizumab in the same indication on a compassionate basis since February 2021 may also be retrospectively included in the cohort.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Identification of predictive factors of resistance to pembrolizumab in first-line treatment of MSI and/or dMMR metastatic colorectal cancer
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bayonne CEDEX
country: France
facility: Ch - Centre Hospitalier de La Côte Basque
city: Beauvais
country: France
facility: Ch - Ch Beauvais
city: Besançon
country: France
facility: CH Jean Minjoz
city: Boujan-sur-Libron
country: France
facility: Polyclinique Saint Privat
city: Boulogne-sur-Mer
country: France
facility: Ch - Duchenne
city: Chambéry CEDEX
country: France
facility: Ch - Centre Hospitalier Metropole Savoie
city: Cholet
country: France
facility: Ch - Centre Hospitalier de Cholet
city: Compiègne
country: France
facility: CH - Compiegne
city: La Roche-sur-Yon
country: France
facility: Ch - Chd Vendée
city: Le Coudray
country: France
facility: CH - Louis Pasteur
city: Lille
country: France
facility: Centre Hospitalier Regional et Universitaire de Lille
city: Lyon
country: France
facility: CH Saint Joseph - Saint Luc
city: Lyon
country: France
facility: Caluire et Cuire - Infirmerie Protestante de Lyon
city: Marseille
country: France
facility: Ch - Hôpital Saint Joseph
city: Marseille
country: France
facility: CH Saint Joseph
city: Mulhouse
country: France
facility: Centre Hospitalier
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Prive - Institut Montsouris
city: Soissons CEDEX
country: France
facility: Ch - Centre Hospitalier de Soisson
city: Tourcoing
country: France
facility: CH - Gustave Dron
Study officials:
affiliation: Hôpital Européen Georges Pompidou APHP
name: Aziz ZAANAN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: