Non-small cell lung cancer is a highly prevalent malignancy, whose social and economic burden have raised substantially in the previous decades. Novel progresses in the biological field have allowed the development of treatments aiming at regulatory check-points of our immune system. These new developments are shedding a hope towards an improvement in the quality of life and prognosis of affected individuals. Importantly, phase II studies have brought first evidences that a combination of two immune check points regulators, Ipilimumab and Nivolumab, could improve the overall prognosis of this disease. We describe a study design for a multicenter, randomized, phase II, open-label clinical trial which aims to compare the superiority of the combination Ipilimumab and Nivolumab versus chemotherapy (Pemetrexate-Cisplatin) in patients with advanced non-squamous non-small cell lung cancer naive to treatment.