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Combining chemotherapy and immunotherapy for metastatic colorectal cancer with high immune infiltration

Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study

Phase 2 Interventional Federation Francophone de Cancerologie Digestive · NCT04262687

This study is testing if combining chemotherapy with an immunotherapy drug can help people with advanced colorectal cancer that has come back after treatment.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment55 (estimated)
Ages18 Years and up
SexAll
SponsorFederation Francophone de Cancerologie Digestive Academic / other
Drugs / interventionschemotherapy, immunotherapy, prednisone, Pembrolizumab
Locations88 sites (Abbeville and 87 other locations)
Trial IDNCT04262687 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining chemotherapy agents like Capecitabine and Oxaliplatin with the immunotherapy drug Pembrolizumab in treating patients with microsatellite stable (MSS) metastatic colorectal cancer that shows high immune infiltration. The study aims to evaluate the immune response in patients who have previously undergone treatment for their primary tumor and have experienced a recurrence. Participants must have measurable metastatic disease and meet specific health criteria to ensure they can tolerate the treatment regimen.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically proven MSS metastatic colorectal adenocarcinoma and high immune infiltration.

Not a fit: Patients with microsatellite unstable (MSI) colorectal cancer or those who do not meet the specific health criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option that enhances the immune response against colorectal cancer, potentially improving patient outcomes.

How similar studies have performed: Other studies have shown promising results with similar combinations of chemotherapy and immunotherapy in various cancers, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Age ≥ 18 years
* MSS and pMMR metastatic colorectal adenocarcinoma (metachronous or synchronous metastases), histologically proven
* Patients who have had chemotherapy (neo-adjuvant or adjuvant) or radiotherapy (neo-adjuvant or adjuvant) for the treatment of primary tumor or metastatic resected disease R0 can be included if they have a recurrence more than 6 months after the end of this treatment.
* High immune response defined as the immune infiltration scores obtained on the primary tumour (resection of primary tumour containing at least 2 mm of tumour-free margin between the tumour and non-tumour area)
* Unresectable cancer with at least one measurable metastatic target according to RECIST v1.1 criteria
* WHO PS ≤ 1
* Life expectancy ≥ 3 months
* Adequate haematological function: neutrophils ≥ 1,500 /mm3, platelets ≥ 100,000/mm3, Hb \> 9 g/dL
* Adequate liver function: AST/ALT ≤ 5xULN, total bilirubin ≤ 2xULN, alkaline phosphatase. ≤ 5xULN
* Creatinine clearance \> 50 mL/min according to the MDRD formula
* Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour
* Patient who is a beneficiary of the social security system
* Information provided to patient and signature of the informed consent form

Exclusion Criteria:

* Active infection requiring intravenous antibiotics at day 1 of cycle 1
* Active or untreated central nervous system metastases
* Another concomitant cancer or history of cancer during the last 5 years, except for carcinoma in situ of the uterine cervix or a basal cell or squamous cell skin carcinoma or any other carcinoma in situ considered as cured
* Previous bone marrow allogenic stem cell transplantation or previous organ transplantation
* History of idiopathic pulmonary fibrosis, medicinal product-related pneumonia or proof of active pneumonia or pneumonitis on a chest CT-scan prior to therapy
* HIV infection, active hepatitis B or C infection, active tuberculosis
* Colorectal cancer with microsatellite instability (dMMR and/or MSI)
* Patient eligible for curative treatment (resection and/or thermal ablation according to the opinion of the local multidisciplinary tumour meeting board)
* Patient with only primary tumour biopsies available or only a sample of a metastasis (no surgical resection of the primary tumour)
* Previous treatment with anti-PD1 or anti-PDL1 or another immunotherapy
* An auto-immune disease which may worsen during treatment with an immune-stimulating agent (patients with type I diabetes, vitiligo, psoriasis, hypo or hyperthyroidism not requiring immunosuppressant therapy are eligible)
* Long-term immunosuppressant therapy (patients requiring corticosteroid therapy are eligible if administration at a dose ≤ 10 mg prednisone equivalent dose per day, administration of steroids by a route of administration resulting in minimal systemic exposure (cutaneous, rectal, ocular or inhalation) is authorised)
* Known severe hypersensitivity to monoclonal antibodies, to one of the medicinal products used or to one of the excipients in the products used or a history of anaphylactic shock or of uncontrolled asthma
* Vaccinations (live vaccine) within 30 days prior to start of treatment
* Dihydropyrimidine Dehydrogenase (DPD) deficiency defined by uracilemy level ≥ 16 ng/mL
* QT/QTc interval \> 450 msec in men and \> 470 msec in women
* One of the following disorders during the 6 months prior to inclusion: myocardial infarction, unstable/severe angina pectoris, coronary artery bypass grafting, NYHA class II, III or IV congestive heart failure, stroke or transient ischaemic attack
* All uncontrolled progressive disorders during the last 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency, arterial hypertension
* History of an inflammatory digestive disease, obstruction or sub-obstruction not resolved with symptomatic treatment
* Peptic ulcer disease not healed before the treatment
* Not controlled HTA
* Patient already enrolled in another therapeutic trial with an ongoing investigational drug or whose treatment ended less than 4 weeks before inclusion
* Absence of effective contraception in patients (male and/or female patients) of childbearing potential, a pregnant or breastfeeding woman, women of childbearing potential and who have not had a pregnancy test
* Impossibility to submit to medical follow-up of the trial due to geographic, social or psychological reasons

Where this trial is running

Abbeville and 87 other locations

+38 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Colorectal Cancer MetastaticHigh Immune InfiltrateMicrosatellite Stableimmunotherapyimmune infiltratefirst line
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.