Background: The combination of avelumab plus axitinib has been recently reported to be superior than sunitinib alone for treatment of previously untreated mRCC patients (Motzer, NEJM 2019). The study reported a median PFS of 13.8 for the combination of avelumab plus axitinib compared to 8.4 months for sunitinib (p<0.001) with an ORR of 48% vs 24%, respectively. To improve treatment efficacy and safety, TKI discontinuation has been considered in patients treated with sunitinib leading to a longer definitive progression free survival (22.4 months) and overall survival (34.8 months) with a better safety profile (Ornstein, JCO 2017). Despite a new tumor response at TKI reintroduction, many patients progressed after the first months of treatment discontinuation suggesting the necessity to maintain the previous response. This study aims to test if patients achieving a tumor response with the combination of avelumab plus axitinib, can discontinue the TKI in order to delay the resistance and decrease the toxicity related to the combination of therapies. Methods: The single arm, phase II TIDE-A trial, aims to evaluate the activity of avelumab as maintenance therapy in patients with mRCC who achieved a tumor response after the induction phase of therapy with the combination of avelumab and axitinib. Eligible patients have clear cell carcinoma, ECOG performance status 0 or 1, measurable, no bulky disease without tumor-related symptoms or hepatic metastases. Eligible patient will receive the combination of avelumab plus axitinib for 36 weeks. Patients achieving RECIST 1.1 partial response discontinue the axitinib and continue avelumab. At tumor progression, the axitinib will be restarted for at least six months. If a new tumor response is achieved, axitinib will be discontinued again until tumor progression. Patients with RECIST 1.1 stable disease continue the combination of avelumab and axitinib until progression of disease. The primary endpoint is to evaluate the rate of patients free of progression after 8 weeks from axitinib discontinuation. The study is currently ongoing in twenty centres in Italy.