Background: Despite recent advances in drug therapy, pts with mRCC have about a 10% 5-year survival rate. Several preclinical studies have documented an increase in peripheral antitumour immunity following radiation, a phenomenon known as the abscopal effect. NIVO is an anti-programmed cell death-1 (PD-1) monoclonal antibody that blocks tumour growth in different ways by targeting certain cells. It might work even better when combined with SBRT. The irradiated tumour cell death can enhance antitumor immunity by inducing antigen expression on tumour cells and activating lymphocytes. The aim of the study is to evaluate whether the antitumour immunity of NIVO can be enhanced by SBRT. Methods: This is an ongoing phase II, single arm, multicentre study in pts with mRCC with progression disease after ≤ 2 prior anti-angiogenic therapies and with 2 or more measurable non-brain metastatic sites, at least one of which potentially suitable for treatment with SBRT. All pts will receive hypofractionated radiation at a lesion at a dose and schedule of 10 Gy/3 fractions respectively after 7 days from the first infusion of NIVO. NIVO will be given as flat dose of 240 mg in intravenous infusion beginning on day 1 every 14 days for 6 months, then switch to 480 mg q4-weekly in responding (CR, PR, SD) pts until PD or unacceptable toxicity. The primary objective is to evaluate the activity of this combination in terms of Objective Response Rate (ORR), the best response recorded on the ITT population according to RECIST v1.1. Our hypothesis is that treatment with NIVO plus SBRT compared to NIVO monotherapy can increase the ORR from 25% to 40%. Secondary endpoints are progression free survival (PFS), overall survival (OS), ORR of irradiated and non-irradiated metastases, duration of response and safety profile. An Exploratory Project also identifies molecular basis of synergistic effect of SBRT and immunotherapy, potential mechanisms of resistance to checkpoint inhibitors. Twenty of the planned 68 pts were enrolled from July 2017 to January 2018. Study duration will be 12 months for the accrual and 36 months for the follow-up. Clinical trial information: EudraCT Num 2016-003032-20. Clinical trial information: EudraCT Number 2016-003032-20.