***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE Programmed death-1 ( PD-1 ) , an inhibitory receptor expressed on activated T cells , may suppress antitumor immunity . This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity , pharmacodynamics , and immunologic correlates . PATIENTS AND METHODS Thirty-nine patients with advanced metastatic melanoma , colorectal cancer ( CRC ) , castrate-resistant prostate cancer , non-small-cell lung cancer ( NSCLC ) , or renal cell carcinoma ( RCC ) received a single intravenous infusion of  anti-PD-1 ( MDX-1106 ) in dose-escalating six-patient cohorts at 0.3 , 1 , 3 , or 10 mg/kg , followed by a 15-patient expansion cohort at 10 mg/kg . Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy . RESULTS Anti-PD-1 was well tolerated : one serious adverse event , inflammatory colitis , was observed in a patient with melanoma who received five doses at 1 mg/kg . One durable complete response ( CRC ) and two partial responses ( PRs ; melanoma , RCC ) were seen . Two additional patients ( melanoma , NSCLC ) had significant lesional tumor regressions not meeting PR criteria . The serum half-life of anti-PD-1 was 12 to 20 days . However , pharmacodynamics indicated a sustained mean occupancy of > 70 % of PD-1 molecules on circulating T cells > or = 2 months following infusion , regardless of dose . In nine patients examined , tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment . CONCLUSION Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity . Exploration of alternative dosing regimens and combinatorial therapies with vaccines , targeted therapies , and /or other checkpoint inhibitors is warranted BACKGROUND Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma . We aim ed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma . METHODS We undertook a r and omised , double-blind , phase 2 trial in 66 centres from 12 countries . 217 patients with previously treated stage III ( unresectable ) or stage IV melanoma were r and omly assigned a fixed dose of ipilimumab of either 10 mg/kg ( n=73 ) , 3 mg/kg ( n=72 ) , or 0.3 mg/kg ( n=72 ) every 3 weeks for four cycles ( induction ) followed by maintenance therapy every 3 months . R and omisation was done with a permuted block procedure , stratified on the basis of type of previous treatment . The primary endpoint was best overall response rate ( the proportion of patients with a complete or partial response , according to modified WHO criteria ) . Efficacy analyses were done by intention to treat , whereas safety analyses included patients who received at least one dose of ipilimumab . This study is registered with Clinical Trials.gov , number NCT00289640 . FINDINGS The best overall response rate was 11.1 % ( 95 % CI 4.9 - 20.7 ) for 10 mg/kg , 4.2 % ( 0.9 - 11.7 ) for 3 mg/kg , and 0 % ( 0.0 - 4.9 ) for 0.3 mg/kg ( p=0.0015 ; trend test ) . Immune-related adverse events of any grade arose in 50 of 71 , 46 of 71 , and 19 of 72 patients at doses of 10 mg/kg , 3 mg/kg , and 0.3 mg/kg , respectively ; the most common grade 3 - 4 adverse events were gastrointestinal immune-related events ( 11 in the 10 mg/kg group , two in the 3 mg/kg group , none in the 0.3 mg/kg group ) and diarrhoea ( ten in the 10 mg/kg group , one in the 3 mg/kg group , none in the 0.3 mg/kg group ) . INTERPRETATION Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma , lending support to further studies at a dose of 10 mg/kg . FUNDING Bristol-Myers Squibb 
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Nivolumab concentrations ranged from 35 to 150 ng/ml in CSF of these patients , which is in the range of the half maximal effective concentration ( EC50 ) of 0.64 nM. Conclusions Ipilimumab and nivolumab are active in melanoma brain metastases .
Nivolumab penetrates into the CSF .