NCT06353854

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for all trials

Timeline
46mo left

Started Feb 2024

Longer than P75 for all trials

Geographic Reach
1 country

20 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress37%
Feb 2024Feb 2030

Study Start

First participant enrolled

February 12, 2024

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 28, 2024

Completed
12 days until next milestone

First Posted

Study publicly available on registry

April 9, 2024

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 12, 2029

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 12, 2030

Last Updated

October 6, 2025

Status Verified

October 1, 2025

Enrollment Period

5 years

First QC Date

March 28, 2024

Last Update Submit

October 1, 2025

Conditions

Keywords

immunotherapy resistance

Outcome Measures

Primary Outcomes (1)

  • Identification of predictive factors of resistance to pembrolizumab in first-line treatment of MSI and/or dMMR metastatic colorectal cancer

    Primary resistance will be defined as immediate progression of the disease (at the time of the first assessment, excluding pseudoprogression) Secondary resistance will be defined as progression occurring after control of the disease.

    2 years

Study Arms (2)

Retrospective group

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

Prospective group

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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.

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Ch - Centre Hospitalier de La Côte Basque

Bayonne, 64100, France

NOT YET RECRUITING

Ch - Ch Beauvais

Beauvais, France

NOT YET RECRUITING

CH Jean Minjoz

Besançon, 25030, France

NOT YET RECRUITING

Polyclinique Saint Privat

Boujan-sur-Libron, 34760, France

RECRUITING

Ch - Duchenne

Boulogne-sur-Mer, France

NOT YET RECRUITING

Ch - Centre Hospitalier Metropole Savoie

Chambéry, 73011, France

NOT YET RECRUITING

Ch - Centre Hospitalier de Cholet

Cholet, 49300, France

NOT YET RECRUITING

CH - Compiegne

Compiègne, France

NOT YET RECRUITING

Ch - Chd Vendée

La Roche-sur-Yon, 85925, France

NOT YET RECRUITING

CH - Louis Pasteur

Le Coudray, France

NOT YET RECRUITING

Centre Hospitalier Regional et Universitaire de Lille

Lille, 59037, France

RECRUITING

CH Saint Joseph - Saint Luc

Lyon, 69365, France

NOT YET RECRUITING

Caluire et Cuire - Infirmerie Protestante de Lyon

Lyon, France

NOT YET RECRUITING

Ch - Hôpital Saint Joseph

Marseille, 13285, France

NOT YET RECRUITING

CH Saint Joseph

Marseille, France

NOT YET RECRUITING

Centre Hospitalier

Mulhouse, 68070, France

NOT YET RECRUITING

CHR D'Orleans - Hopital de la Source

Orléans, 45100, France

NOT YET RECRUITING

Prive - Institut Montsouris

Paris, France

RECRUITING

Ch - Centre Hospitalier de Soisson

Soissons, 02209, France

NOT YET RECRUITING

CH - Gustave Dron

Tourcoing, France

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor samples archived for retrospective cohort Tumour samples archived and blood samples at 3 time points for prospective cohort

Study Officials

  • Aziz ZAANAN, MD, PhD

    Hôpital Européen Georges Pompidou APHP

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Aziz ZAANAN, MD, PhD

CONTACT

Leathicia NDONG, MD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2024

First Posted

April 9, 2024

Study Start

February 12, 2024

Primary Completion (Estimated)

February 12, 2029

Study Completion (Estimated)

February 12, 2030

Last Updated

October 6, 2025

Record last verified: 2025-10

Locations