In patients with advanced melanoma, talimogene laherparepvec ( T – VEC ) plus ipilimumab has shown to have greater antitumor activity compared to the drug alone, without any additional toxicity. We present the 5-year results of a randomized phase II study here. For patients with melanoma who have received treatment that combines an oncolytic virus and a checkpoint inhibitor, these data offer the longest efficacy and safety follow-up.
Patients with unresectable stage IIIB-IV melanoma were randomly assigned to receive either ipilimumab alone or T-VEC plus. T-VEC was given intralesionally at 106 plaque-forming units( PFU ) per milliliters in week 1, 108 PFU / mL in weeks 4, and every two weeks after that. Starting in week 1 for the ipilimumab arm and week 6 in the combination arm, IVIMUMABAb( 3 mg / kg every 3 weeks, & le, 4 doses ) was given intravenously. Key secondary end points included durable response rate( DRR ), duration of response ( DOR ), progression-free survival ( PFS ), overall survival, and safety. The primary end point was investigator-assessed objective response rating( ORR ) per immune-related response criteria.
In total, 198 patients were randomly assigned to receive either the ipilimumab( n = 100 ) or the combination( N = 98 ). The ORR versus ipilimumab( 35.7 % vs. 16.0 %, OR 2.9, 95 % CI 1.5 to 5.7, p = 0.003 ) was improved by the combination. ( Unadjusted OR 3.4, 95 % CI 1.7 to 7.0, descriptive p = 0.001 ) and DRR were 33.7 % and 13.0 %, respectively. With the combination and ipilimumab, the median DOR among the objective responders was 69.2 months( 95 % CI 38.5 to not estimable ). Median PFS was 13.5 % with the combination and 6.4 % with ipilimumab( HR 0.78, 95 % CI 0.55 to 1.09, descriptive p = 0.14 ). Estimated 5-year OS was 48.4 %( 95 % CI 37.9 to 58.1 ) in the ipilimumab arm and 54.7 %( 43.9 to 64.2 ) in combination arm. Patients in the combination and ipilimumab arms received subsequent therapies for 47 ( 48.0 %) and 65 ( 65.0 %), respectively. There were no new safety alerts reported.
At the 5-year follow-up, the improved response rates observed with T-VEC plus ipilimumab were durable. This is the first randomized controlled study of the combination of an oncolytic virus and a checkpoint inhibitor that meets its primary end point.Trial registration number: NCT01740297.