***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 : Tremelimumab , a fully human cytotoxic T-lymphocyte antigen 4 monoclonal antibody , and PF-3512676 , a Toll-like receptor-9 agonist , are targeted immune modulators that elicit durable single-agent antitumour activity in advanced cancer . Methods : To determine the maximum tolerated dose ( MTD ) of these agents combined during this phase I study , patients received intravenous tremelimumab ( 6.0 , 10.0 , or 15.0 mg kg−1 ) every 12 weeks plus subcutaneous PF-3512676 ( 0.05 , 0.10 , or 0.15 mg kg−1 ) weekly . Primary end points were safety and tolerability ; secondary end points included pharmacokinetics and antitumour activity . Results : Twenty-one patients with stage IV melanoma ( n=17 ) or advanced solid tumours ( n=4 ) were enrolled . Injection-site reactions ( n=21 ; 100 % ) , influenza-like illness ( n=18 ; 86 % ) , and diarrhoea ( n=13 ; 62 % ) were the most common treatment-related adverse events ( TAEs ) . Grade ⩾3 TAEs were reported ( n=7 ; 33 % ) . Dose-limiting toxicities ( prespecified 6-week observation ) occurred in one of the six patients in the 10 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 cohort ( grade 3 hypothalamopituitary disorder ) and two of the six patients in the 15 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 cohort ( grade 3 diarrhoea ) . Consequently , 15 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 exceeded the MTD . Two melanoma patients achieved durable ( ⩾170 days ) partial response . No human antihuman antibody responses to tremelimumab were observed . Conclusion : Weekly PF-3512676 ( ⩽0.15 mg kg−1 ) plus tremelimumab ( ⩽10 mg kg−1 every 12 weeks ) was tolerable BACKGROUND Treatments for small-cell lung cancer ( SCLC ) after failure of platinum-based chemotherapy are limited . We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens . METHODS The SCLC cohort of this phase 1/2 multicentre , multi-arm , open-label trial was conducted at 23 sites ( academic centres and hospitals ) in six countries . Eligible patients were 18 years of age or older , had limited-stage or extensive-stage SCLC , and had disease progression after at least one previous platinum-containing regimen . Patients received nivolumab ( 3 mg/kg bodyweight intravenously ) every 2 weeks ( given until disease progression or unacceptable toxicity ) , or nivolumab plus ipilimumab ( 1 mg/kg plus 1 mg/kg , 1 mg/kg plus 3 mg/kg , or 3 mg/kg plus 1 mg/kg , intravenously ) every 3 weeks for four cycles , followed by nivolumab 3 mg/kg every 2 weeks . Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg . Depending on tolerability , patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . The primary endpoint was objective response by investigator assessment . All analyses included patients who were enrolled at least 90 days before data base lock . This trial is ongoing ; here , we report an interim analysis of the SCLC cohort . This study is registered with Clinical Trials.gov , number NCT01928394 . FINDINGS Between Nov 18 , 2013 , and July 28 , 2015 , 216 patients were enrolled and treated ( 98 with nivolumab 3 mg/kg , three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg ) . At data base lock on Nov 6 , 2015 , median follow-up for patients continuing in the study ( including those who had died or discontinued treatment ) was 198·5 days ( IQR 163·0 - 464·0 ) for nivolumab 3 mg/kg , 302 days ( IQR not calculable ) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 361·0 days ( 273·0 - 470·0 ) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 260·5 days ( 248·0 - 288·0 ) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . An objective response was achieved in ten ( 10 % ) of 98 patients  receiving nivolumab 3 mg/kg , one ( 33 % ) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 14 ( 23 % ) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and ten ( 19 % ) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . Grade 3 or 4 treatment-related adverse events occurred in 13 ( 13 % ) patients in the nivolumab 3 mg/kg cohort , 18 ( 30 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort , and ten ( 19 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( none vs 5 [ 8 % ] vs none ) and diarrhoea ( none vs 3 [ 5 % ] vs 1 [ 2 % ] ) . No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event . Six ( 6 % ) patients in the nivolumab 3 mg/kg group , seven ( 11 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group , and four ( 7 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events . Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events ( myasthenia gravis and worsening of renal failure ) , and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis . INTERPRETATION Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC . These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 r and omised controlled trials in SCLC . FUNDING Bristol-Myers Squibb BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 .  Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer .  Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Pre clinical data suggest that combining a checkpoint inhibition with immunomodulatory derivative can increase anticancer response . We design ed a dose-escalation study using a 3 + 3 design to determine the safety , maximum tolerated dose ( MTD ) or recommended phase II dose ( R2PD ) and dose-limiting toxicities ( DLT ) of the anti – CTLA-4 antibody ipilimumab ( 1.5–3 mg/kg intravenously every 28 days × 4 ) and lenalidomide ( 10–25 mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity ) in advanced cancers . Total of 36 patients ( Hodgkin lymphoma , 7 ; melanoma , 5 ; leiomyosarcoma , 4 ; renal cancer , 3 ; thyroid cancer , 3 ; other cancers , 14 ; median of 3 prior therapies ) were enrolled . The MTD has not been reached and ipilimumab 3 mg/kg and lenalidomide 25 mg have been declared as R2PD . DLT were grade ( G ) 3 rash ( 3 patients ) and G3 pancreatitis ( 1 patient ) . G3/4 drug-related toxicities other than DLT were G3 anemia ( 5 patients ) , G3 thromboembolism ( 2 patients ) , G3 thrombocytopenia , G3 rash , G3 hypopituitarism , G3 pneumonitis , G3 transaminitis , and G4 hypopituitarism ( all in 1 patient ) . Eight patients had tumor shrinkage per immune-related response criteria ( −79 % to −2 % ) including a PR ( −79 % for 7.2 + months ) in a refractory Hodgkin lymphoma . Using comprehensive genomic profiling , a total mutation burden ( mutations/Mb ) was evaluated in 17 patients , with one of the patients achieving a PR demonstrated intermediate mutation burden . In conclusion , combination of ipilimumab and lenalidomide is well tolerated and demonstrated preliminary signals of activity in patients with refractory Hodgkin lymphoma and other advanced cancers . Mol Cancer Ther ; 17(3 ) ; 671–6 . © 2017 AACR Purpose Classical Hodgkin lymphoma ( HL ) frequently exhibits genetic alterations leading to overexpression of the programmed death-1 ( PD-1 ) lig and s , suggesting a possible vulnerability to PD-1 blockade . The phase Ib study KEYNOTE-013 ( NCT01953692 ) tested the safety and efficacy of the anti-PD-1 antibody pembrolizumab in patients with hematologic malignancies . Based on its genetics , HL was included as an independent cohort . Methods We enrolled patients with relapsed or refractory HL whose disease progressed on or 
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Although the rates of these events were low , the risk was increased following ICI-based treatment , particularly for CTLA-4 inhibitors , which were associated with a higher incidence of pituitary-adrenal dysfunction than PD-1/PD-L1 inhibitors