METIMMOX-2: Metastatic pMMR/MSS Colorectal Cancer - Shaping Anti-Tumor Immunity by Oxaliplatin
Hypothesis: Patients with metastatic colorectal cancer with DNA mismatch repair-proficient (pMMR) function / microsatellite-stable (MSS) phenotype harbor a non-immunogenic disease that can be transformed into an immunogenic condition by short-course oxaliplatin-based therapy, and may achieve durable disease control or even tumor eradication by the addition of immune checkpoint blockade therapy to the standard-of-care oxaliplatin-based treatment.
• Patient has histologically verified pMMR/MSS colorectal 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 is at least 18 years of age.
• Patient has radiologically measurable metastatic disease.
• Patient has an infradiaphragmatic metastatic lesion that can be biopsied.
• Patient has not had previous systemic cytotoxic therapy for the metastatic disease, except for previous neoadjuvant treatment.
• Patient is eligible for the Nordic FLOX regimen when it would be the preferred treatment option for first-line therapy in routine practice.
• 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 x10(9)/L (without current use of colony-stimulating factors).
⁃ Platelets at least 100 x10(9)/L. - C-reactive protein less than 60 mg/L
⁃ AST/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. o Bilirubin no higher than 1.5xULN when patient does not have metastatic disease in the liver or no higher than 2xULN when patient has metastatic disease in the liver
⁃ Albumin no lower than 30 g/L. - INR within normal level
⁃ Creatinine no higher than 1.5xULN
• 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
• 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
• Signed informed consent form and expected cooperation of the patients for the treatment and follow-up must be obtained and documented according to International Conference on Harmonization - Good Clinical Practice and national/local regulations