Chemotherapy and Immunotherapy as Treatment for MSS Metastatic Colorectal Cancer With High Immune Infiltrate (POCHI)

This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring immunotherapy, immune infiltrate, first line Read More

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