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Background: L-BLP25 is a MUC1 antigen specific cancer immunotherapy.We report results from the phase Ⅲ START study of L-BLP25 in patients(pts)not progressing after primary chemoradiotherapy(CRT)for stage Ⅲ NSCLC.Methods: From Jan 2007 to Nov 2011,1513 pts with unresectable stage Ⅲ NSCLC that did not progress after CRT(platinum based chemo and ≥50 Gy)were randomized(2:1; double-blind)to L-BLP25(806 μg lipopeptide)or placebo(PBO)SC weekly x 8 then Q6 weeks until disease progression or withdrawal.Cyclophosphamide 300 mg/m2 x 1 or saline was given 3 days prior to first L-BLP25/PBO dose.Primary endpoint was overall survival(OS).Results: The primary analysis population(n=1239)was defined prospectively to try to account for a clinical hold by excluding pts randomized 6 months(m)before the hold.Arms were balanced for baseline characteristics.Median age was 61 y; 38.2%had stage ⅢA and 61.3%ⅢB; 65%had concurrent and 35%sequential CRT.Median OS was 25.6 m with L-BLP25 vs.22.3 m with PBO(adjusted HR 0.88,95%CI 0.75-1.03,p=0.123).Secondary endpoints time-to-progression and time-to-symptom-progression support consistency of Results: HR 0.87(95%CI 0.75-1.00,p=0.053)and 0.85(95%CI 0.73-0.98,p=0.023).In predefined subgroup analyses,pts with concurrent CRT(n=806)had median OS of 30.8 m(L-BLP25)vs.20.6 m(PBO; HR 0.78,95%CI 0.64-0.95,p=0.016),while median OS with sequential CRT was 19.4 m(L-BLP25)vs.24.6 m(PBO; HR 1.12,95%CI 0.87-1.44,p=0.38; interaction p=0.032,Cox PH model).Sensitivity analyses revealed that there was no OS benefit in pts randomized 6 m before the hold(HR 1.09,CI 0.75-1.56,p=0.663).LEBLP25 was well tolerated with no safety concerns identified and no emergent evidence of immune related adverse events.Conclusions: L-BLP25 maintenance therapy in stage Ⅲ NSCLC was well tolerated,but did not significantly prolong OS.Sensitivity analyses showed a smaller treatment effect due to the clinical hold,suggesting that longer uninterrupted treatment with L-BLP25 is required.Clinically meaningful prolongation of OS was observed in the predefined subgroup of pts with primary concurrent CRT.