METIMMOX: Colorectal Cancer METastasis - Shaping Anti-tumor IMMunity by OXaliplatin

Inclusion Criteria

• Patient has histologically verified CRC adenocarcinoma (also comprising the mucinous adenocarcinoma and signet-ring cell carcinoma entities).
• Patient is ambulatory with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patient has radiologically measurable metastatic disease.
• Patient has an intra-abdominal metastatic lesion that can be biopsied.
• Patient has not had previous systemic therapy for the metastatic disease.
• Patient is eligible for the Nordic FLOX regimen.
• Patient has the following laboratory values, as measured in serum/plasma within 14 days prior to study entry, indicative of adequate organ function:
• Hemoglobin at least 10.0 g/dL.
• Neutrophils at least 1.5 x109/L (without current use of colony-stimulating factors).
• Platelets at least 100 x109/L.
• C-reactive protein (CRP) less than 60 mg/L.
• Aspartate transaminase (AST)/Alanine transaminase (ALT) no higher than 2xULN when patient does not have metastatic disease in the liver or no higher than 5xULN when patient has metastatic disease in the liver.
• Bilirubin no higher than 1.5x ULN when patient does not have metastatic disease in the liver or no higher than 2x upper limit of normal (ULN) when patient has metastatic disease in the liver.
• Albumin no lower than 30 g/L.
• International Normalised Ratio (INR) within normal level.
• Creatinine no higher than 1.5x ULN.
• Woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
• WOCBP will use an adequate method to avoid pregnancy for a period of 26 weeks (which includes the required 30 days plus the time required for nivolumab to undergo five half-lives) after the last therapy dose, irrespective of study arm.
• Woman is not breastfeeding.
• Male who is sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 26 weeks (which includes the required time to ensure duration of sperm turnover plus the time required for the investigational drugs to undergo five half-lives) after the last therapy dose, irrespective of study arm.
• Signed informed consent form (ICF) and expected cooperation of the patients for the treatment and follow-up must be obtained and documented according to International Conference on Harmonization (ICH) - Good Clinical Practice (GCP) and national/local regulations.

Exclusion Criteria

• Patient has initially resectable metastatic disease for which neoadjuvant therapy is deemed superfluous.
• Patient does not consent to biopsy sampling.
• Patient has metastatic disease to lungs as the sole site.
• Patient has untreated or symptomatic brain metastasis (patient must be symptom-free without the use of corticosteroids).
• Patient experiences a period of less than 6 months since discontinuation of adjuvant oxaliplatin-containing chemotherapy.
• Patient is ineligible for full chemotherapy doses (100% doses) at start of study treatment.
• Patient has had radiation therapy against the only measurable lesion within 4 weeks of start of study treatment.
• Patient has any medical condition treated with anticoagulant medication that cannot be replaced by low molecular weight heparin during active study treatment.
• Patient has a nervous system disorder worse than Common Terminology Criteria for Adverse Events (CTCAE) grade 1.
• Patient has any medical condition that will preclude him/her from cancer immune-modulating therapy, such as:
• Active or chronic hepatitis B or hepatitis C.
• Known history of human immunodeficiency virus or acquired immunodeficiency-related illnesses.
• Diagnosis of immunodeficiency or medical condition requiring systemic steroids or other forms of immunosuppressive therapy.
• Autoimmune disease that has required systemic therapy within the past 2 years.
• Receipt of live attenuated vaccination within 30 days prior to study entry or within