Background: Uveal melanoma is the most common primary intraocular malignant tumor in adults. Overall survival (OS) at 5 years is 62% due to high incidence of liver metastasis that are fatal within 4 -9 months from diagnosis. No standard treatment exists for MUM. Ipilimumab has demonstrated to improve both overall and long-term survival in patients with advanced cutaneous melanoma (Hodi FS, et al., NEJM 2010; Robert C, et al., NEJM 2011). However, MUM patients were excluded in these trials. Methods: GEM-1 (EudraCT 2010-024415-14) is an open label, single arm phase 2 trial that evaluates first line ipilimumab in adult pts with MUM.The study was conducted in 5 centers in Spain, belonging to the Spanish Melanoma Group (GEM). Eligible pts had progressive metastatic disease, ECOG-PS 0 or 1, and no prior systemic treatment for MUM. Treatment consisted of ipilimumab 10 mg/kg iv q3 weeks (wk) for 4 doses (induction) followed by q12 wk (maintenance) until progression, intolerance or withdrawal. Primary end point was OS and secondary PFS, OR and safety using immune response criteria. Results: 32 pts were enrolled from July 2011 to May 2013. One patient was ineligible due to absence of metastatic disease at baseline. An interim analysis showed preliminary data from the 31 patients. 18 pts were men, mean age (SD) 60 (10). 64.5% (20) and 35.5% (11) of pts were ECOG-PS 0 and 1 respectively and progressive liver metastasis at baseline were present in 25 pts (80.7%) being frequently multiple and affecting both lobes. Ten pts experienced G3 (abdominal pain, hypophysitis (3), emesis, diarrhoea, asthenia, proctalgia, bone pain and urinary tract infection) and 5 pts had G4 toxicities (hepatotoxicity (2), multi-organ failure, altered state of consciousness, and vascular compression). With a median follow-up of 5.5 (CI 95%: 3.4-11.1) months 13 pts were evaluable for response: 1 PR (7.7%) and 6 pts SD (46.2%). Mature OS and PFS data are expected by April 2014. Conclusions: This is the first ipilimumab clinical trial showing preliminary activity in MUM pts. Safety profile is similar to prior reports in cutaneous melanoma. Response rate seems promising while mature OS and PFS results are pending. Clinical trial information: 2010-024415-14.