@Article{macau_mods_00003631, author = {Chesney, Jason A. and Puzanov, Igor and Collichio, Frances A. and Singh, Parminder and Milhem, Mohammed M. and Glaspy, John and Hamid, Omid and Ross, Merrick and Friedlander, Philip and Garbe, Claus and Logan, Theodore and Hauschild, Axel and Lebb{\'e}, Celeste and Joshi, Harshada and Snyder, Wendy and Mehnert, Janice M.}, title = {Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial}, journal = {Journal for immunotherapy of cancer}, year = {2023}, publisher = {BMJ}, address = {London}, volume = {11}, number = {5}, keywords = {Humans; Herpesvirus 1, Human; Melanoma; Oncolytic Virotherapy; Oncolytic Viruses; Ipilimumab; Immunotherapy}, abstract = {Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus ipilimumab alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide the longest efficacy and safety follow-up for patients with melanoma treated with a combination of an oncolytic virus and a checkpoint inhibitor.Eligible patients with unresectable stage IIIB‒IV melanoma were randomized 1:1 to receive T-VEC plus ipilimumab or ipilimumab alone. T-VEC was administered intralesionally at 106 plaque-forming units (PFU)/mL in week 1, followed by 108 PFU/mL in week 4 and every 2 weeks thereafter. Ipilimumab (3 mg/kg every 3 weeks; ≤4 doses) was administered intravenously starting at week 1 in the ipilimumab arm and week 6 in the combination arm. The primary end point was investigator-assessed objective response rate (ORR) per immune-related response criteria; key secondary end points included durable response rate (DRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Overall, 198 patients were randomized to receive the combination (n=98) or ipilimumab (n=100). The combination improved the ORR versus ipilimumab (35.7{\%} vs 16.0{\%}; OR 2.9; 95{\%} CI 1.5 to 5.7; p=0.003). DRR was 33.7{\%} and 13.0{\%} (unadjusted OR 3.4; 95{\%} CI 1.7 to 7.0; descriptive p=0.001), respectively. Among the objective responders, the median DOR was 69.2 months (95{\%} CI 38.5 to not estimable) with the combination and was not reached with ipilimumab. Median PFS was 13.5 months with the combination and 6.4 months with ipilimumab (HR 0.78; 95{\%} CI 0.55 to 1.09; descriptive p=0.14). 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.}, issn = {2051-1426}, doi = {10.1136/jitc-2022-006270}, url = {https://macau.uni-kiel.de/receive/macau_mods_00003631}, url = {https://doi.org/10.1136/jitc-2022-006270}, url = {http://www.ncbi.nlm.nih.gov/pubmed/37142291}, file = {:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00004843/e006270.full.pdf:PDF}, language = {en} }