Two Combination Treatment Regimens of Nivolumab and Ipilimumab in Patients With dMMR and / or MSI mCRC.

NIPISAFE is open-label, phase II study to identify a combination scheme of nivolumab and ipilimumab with a high level of clinical activity, but with a lower toxicity in MSI/dMMR metastatic colorectal cancer patients.

This is a randomized non-comparative two-stage phase II study with a co-primary endpoint (toxicity and progression-free survival) to evaluate two different schemes of the nivolumab and ipilimumab combination in terms of the toxicity and efficacy in MSI/dMMR metastatic colorectal cancer patients in order to identify a combination scheme with a higher level of clinical activity and a lower toxicity. Patients will be randomized in a 2:1 ratio to receive one of the following treatments: Experimental ARM A: Nivolumab 480 mg every 4 weeks and ipilimumab 1 mg/kg every 6 weeks for a total of 24 months of treatment Control ARM B: Nivolumab 240 mg and ipilimumab 1 mg/kg every 3 weeks for 4 dosing cycles. Maintenance of 96 weeks: Nivolumab 480 mg every 4 weeks for 24 dosing cycles for a total of 24 months of treatment (or less in case of RECIST PD or limiting toxicity, whichever occurs first).