5018 Background: Patients with rare genitourinary malignancies (Bladder cancer of variant histologies (BCVH), adrenal tumors, chemotherapy refractory germ cell tumors (CRGCT), penile carcinoma and prostate cancer of variant histology (PCVH)) have poor outcomes. Nivolumab and ipilimumab has demonstrated safety and efficacy in genitourinary malignancies. In this multicenter, single arm, multi-cohort phase II trial we evaluated the efficacy of nivolumab and ipilimumab in pts with advanced rare genitourinary cancers (NCT 03333616). Herein, we report the results of the fully accrued BCVH, adrenal and other cohorts. Methods: Eligible pts had a metastatic rare genitourinary malignancy, ECOG performance status of 0-2 and no prior immune checkpoint inhibitor exposure; aside from CRGCT pts could be treatment naïve. Eligible pts received nivolumab 3 mg/kg and ipilimumab 1 mg/kg intravenously every 3 weeks for 4 doses with continued nivolumab 480 mg IV every 4 weeks. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Results: 56 pts were enrolled at 6 institutions between 4/2018 and 7/2019 in 3 cohorts: BCVH (N = 19), adrenal tumors (n = 18) and other tumors (n = 19). Median follow-up was 9.9 (range < 1~21) months. 28(50%) pts received all 4 doses of nivolumab and ipilimumab. 25 pts received nivolumab maintenance at a median of 4 (range 1-18) cycles. ORR in entire cohort was 16% (n = 9: 2 CR 7 PR, Table); 67% of responders (6/9) maintained response greater than 9 months. Median PFS was 2.8 (2.7-5.2) months. 22 pts (39%) developed treatment-related ≥ grade 3 toxicity; 23% required high dose steroids (≥40 mg prednisone or equivalent) and 15 (27%) pts discontinued treatment due to an AE. Grade 5 toxicity occurred in 3 pts; 1 death was treatment related. Conclusions: Nivolumab and ipilimumab resulted in objective responses in a subset of pts with rare GU malignancies, especially in BCVH. Biomarkers are being evaluated and an additional cohort exploring the activity in genitourinary tumors with neuroendocrine differentiation is ongoing. This combination warrants further investigation in these pts with substantial unmet needs. Clinical trial information: NCT 03333616 . [Table: see text]