***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: BACKGROUND Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab ( an anti-PD-1 antibody ) plus ipilimumab ( an anti-CTLA-4 antibody ) compared with ipilimumab alone . We report 2-year overall survival data from a r and omised controlled trial assessing this treatment in previously untreated advanced melanoma . METHODS In this multicentre , double-blind , r and omised , controlled , phase 2 trial ( CheckMate 069 ) we recruited patients from 19 specialist cancer centres in two countries ( France and the USA ) . Eligible patients were aged 18 years or older with previously untreated , unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients were r and omly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo , every 3 weeks for four doses . Subsequently , patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity , whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase . R and omisation was done via an interactive voice response system with a permuted block schedule ( block size of six ) and stratification by BRAF mutation status . The study funder , patients , investigators , and study site staff were masked to treatment assignment . The primary endpoint , which has been reported previously , was the proportion of patients with BRAFV600 wild-type melanoma achieving an investigator-assessed objective response . Overall survival was an exploratory endpoint and is reported in this Article . Efficacy analyses were done on the intention-to-treat population , whereas safety was assessed in all treated patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01927419 , and is ongoing but no longer enrolling patients . FINDINGS Between Sept 16 , 2013 , and Feb 6 , 2014 , we screened 179 patients and enrolled 142 , r and omly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone . In each treatment group , one patient no longer met the study criteria following r and omisation and thus did not receive study drug . At a median follow-up of 24·5 months ( IQR 9·1 - 25·7 ) , 2-year overall survival was 63·8 % ( 95 % CI 53·3 - 72·6 ) for those assigned to nivolumab plus ipilimumab and 53·6 % ( 95 % CI 38·1 - 66·8 ) for those assigned to ipilimumab alone ; median overall survival had not been reached in either group ( hazard ratio 0·74 , 95 % CI 0·43 - 1·26 ; p=0·26 ) . Treatment-related grade 3 - 4 adverse events were reported in 51 ( 54 % ) of 94 patients who received nivolumab plus ipilimumab compared with nine ( 20 % ) of 46 patients who received ipilimumab alone . The most common treatment-related grade 3 - 4 adverse events were colitis ( 12 [ 13 % ] of 94 patients ) and increased alanine aminotransferase ( ten [ 11 % ] ) in the combination group and diarrhoea ( five [ 11 % ] of 46 patients ) and hypophysitis ( two [ 4 % ] ) in the ipilimumab alone group . Serious grade 3 - 4 treatment-related adverse events were reported in 34 ( 36 % ) of 94 patients who received nivolumab plus ipilimumab ( including colitis in ten [ 11 % ] of 94 patients , and diarrhoea in five [ 5 % ] ) compared with four ( 9 % ) of 46 patients who received ipilimumab alone ( including diarrhoea in two [ 4 % ] of 46 patients , colitis in one [ 2 % ] , and hypophysitis in one [ 2 % ] ) . No new types of treatment-related adverse events or treatment-related deaths occurred in this up date d analysis . INTERPRETATION Although follow-up of the patients in this study is ongoing , the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma . The results suggest encouraging survival outcomes with immunotherapy in this population of patients . FUNDING Bristol-Myers Squibb Background Immunotherapies have demonstrated efficacy across a diverse set of tumors supporting further evaluation in glioblastoma . The objective of this study was to evaluate the safety/tolerability and describe immune-mediated effects of nivolumab ± ipilimumab in patients with recurrent glioblastoma . Exploratory efficacy outcomes are also reported . Methods Patients were r and omized to receive nivolumab 3 mg/kg every 2 weeks ( Q2W ; NIVO3 ) or nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks ( Q3W ) for 4 doses , then nivolumab 3 mg/kg Q2W ( NIVO1+IPI3 ) . An alternative regimen of nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W for 4 doses , then nivolumab 3 mg/kg Q2W ( NIVO3+IPI1 ) was investigated in a nonr and omized arm . Results Forty patients were enrolled ( NIVO3 , n = 10 ; NIVO1+IPI3 , n = 10 ; NIVO3+IPI1 , n = 20 ) . The most common treatment-related adverse events ( AEs ) were fatigue ( NIVO3 , 30 % ; NIVO1+IPI3 , 80 % ; NIVO3+IPI1 , 55 % ) and diarrhea ( 10 % , 70 % , 30 % , respectively ) . AEs leading to discontinuation occurred in 10 % ( NIVO3 ) , 30 % ( NIVO1+IPI3 ) , and 20 % ( NIVO3+IPI1 ) of patients . Three patients achieved a partial response ( NIVO3 , n = 1 ; NIVO3+IPI1 , n = 2 ) and 8 had stable disease for ≥12 weeks ( NIVO3 , n = 2 ; NIVO1+IPI3 , n = 2 ; NIVO3+IPI1 , n = 4 [ Response Assessment in Neuro-Oncology criteria ] ) . Most patients ( 68 % ) had tumor-cell programmed death lig and -1 expression ≥1 % . Immune-mediated effects mimicking radiographic progression occurred in 2 patients . Conclusions Nivolumab monotherapy was better tolerated than nivolumab + ipilimumab ; the tolerability of the combination was influenced by ipilimumab dose . These safety and exploratory findings merit further investigation of immunotherapies in glioblastoma BACKGROUND Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC . METHODS The open-label , phase 1 , multicohort study ( CheckMate 012 ) cohorts reported here were enrolled at eight US academic centres . Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV , chemotherapy-naive NSCLC . Patients were r and omly assigned ( 1:1:1 ) by an interactive voice response system to receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks , nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks , or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression , unacceptable toxicities , or withdrawal of consent . Data from the latter two cohorts , which were considered potentially suitable for further clinical development , are presented in this report ; data from the other cohort ( as well as several earlier cohorts ) are described in the appendix . The primary outcome was safety and tolerability , assessed in all treated patients . This ongoing study is registered with Clinical Trials.gov , number NCT01454102 . FINDINGS Between May 15 , 2014 , and March 25 , 2015 , 78 patients were r and omly assigned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks ( n=38 ) or nivolumab every 2 weeks plus ipilimumab every 6 weeks ( n=40 ) . One patient in the ipilimumab every-6-weeks cohort was excluded before treatment ; therefore 77 patients actually received treatment ( 38 in the ipilimumab every-12-weeks cohort ; 39 in the ipilimumab every-6-weeks cohort ) . At data cut-off on Jan 7 , 2016 , 29 ( 76 % ) patients in the ipilimumab every-12-weeks cohort and 32 ( 82 % ) in the ipilimumab every-6-weeks cohort had discontinued treatment . Grade 3 - 4 treatment-related adverse events occurred in 14 ( 37 % ) patients in the ipilimumab every-12-weeks cohort and 13 ( 33 % ) patients in the every-6-weeks cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( three [ 8 % ] and no patients ) , pneumonitis ( two [ 5 % ] and one [ 3 % ] patients ) , adrenal insufficiency ( one [ 3 % ] and two [ 5 % ] patients ) , and colitis ( one [ 3 % ] and two [ 5 % ] patients ) . Treatment-related serious adverse events were reported in 12 ( 32 % ) patients in the ipilimumab every-12-weeks cohort and 11 ( 28 % ) patients in the every-6-weeks cohort . Treatment-related adverse events ( any grade ) prompted treatment discontinuation in four ( 11 % ) patients in the every-12-weeks cohort and five ( 13 % ) patients in the every-6-weeks cohort . No treatment-related deaths occurred . Confirmed objective responses were achieved in 18 ( 47 % [ 95 % CI 31 - 64 ] ) patients in the ipilimumab every-12-weeks cohort and 15 ( 38 % [ 95 % CI 23 - 55 ] ) patients in the ipilimumab every-6-weeks cohort ; median duration of response was not reached in either cohort , with median follow-up times of 12·8 months ( IQR 9·3 - 15·5 ) in the ipilimumab every-12-weeks cohort and 11·8 months ( 6·7 - 15·9 ) in the ipilimumab every-6-weeks cohort . In patients with PD-L1 of 1 % or greater , confirmed objective responses were achieved in 12 ( 57 % ) of 21 patients in the ipilimumab every-12-weeks cohort and 13 ( 57 % ) of 23 patients in the ipilimumab every-6-weeks cohort . INTERPRETATION In NSCLC , first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response . To our knowledge , the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC , supporting further assessment of this combination in a phase 3 study . FUNDING Bristol-Myers Squibb BACKGROUND Tremelimumab , an anti-CTLA4 monoclonal antibody , initially showed good activity when used alone in patients with mesothelioma , but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study . We aim ed to investigate the efficacy and safety of first-line or second-line tremelimumab combined with durvalumab , an anti-PD-L1 monoclonal antibody , in patients with malignant mesothelioma . METHODS In this open-label , non-r and omised , phase 2 trial , patients with unresectable pleural or peritoneal mesothelioma received intravenous tremelimumab ( 1 mg/kg bodyweight ) and durvalumab ( 20 mg/kg bodyweight ) every 4 weeks for four doses , followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses . The primary endpoint was the proportion of patients with an immune-related objective response according to the immune-related modified Response Evaluation Criteria in Solid Tumors ( RECIST ; for pleural mesothelioma ) or immune-related RECIST version 1.1 ( for peritoneal mesothelioma ) . The primary analysis was done by intention to treat , whereas the safety analysis included patients who received at least one dose of study drug . This trial is registered with the European Clinical Trials Data base , number 2015 - 001995 - 23 
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The most common all- grade TRAEs were diarrhea/colitis , fatigue/asthenia , nausea/vomiting , rash , and pruritis .
Conclusion : Combination ICI therapy has a significantly different treatment-related adverse event profile compared to monotherapy