{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:39:50Z","timestamp":1793039990820,"version":"4.5.0"},"reference-count":18,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"unspecified","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen Inc","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,3,31]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>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.<\/jats:p>\n                  <jats:p>\n                    Eligible patients with unresectable stage IIIB\u2012IV melanoma were randomized 1:1 to receive T-VEC plus ipilimumab or ipilimumab alone. T-VEC was administered intralesionally at 10\n                    <jats:sup>6<\/jats:sup>\n                    plaque-forming units (PFU)\/mL in week 1, followed by 10\n                    <jats:sup>8<\/jats:sup>\n                    PFU\/mL in week 4 and every 2 weeks thereafter. Ipilimumab (3 mg\/kg every 3 weeks; \u22644 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.\n                  <\/jats:p>\n                  <jats:p>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). Estimated 5-year OS was 54.7% (95% CI 43.9 to 64.2) in the combination arm and 48.4% (95% CI 37.9 to 58.1) in the ipilimumab arm. Forty-seven (48.0%) and 65 (65.0%) patients in the combination and ipilimumab arms, respectively, received subsequent therapies. No new safety signals were reported.<\/jats:p>\n                  <jats:p>\n                    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:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01740297\">NCT01740297<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1136\/jitc-2022-006270","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T11:01:43Z","timestamp":1683198103000},"page":"e006270","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":95,"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"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct01740297","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01740297","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-8278","authenticated-orcid":false,"given":"Jason A","family":"Chesney","sequence":"first","affiliation":[{"name":"J. Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-3497","authenticated-orcid":false,"given":"Igor","family":"Puzanov","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances A","family":"Collichio","sequence":"additional","affiliation":[{"name":"The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parminder","family":"Singh","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M","family":"Milhem","sequence":"additional","affiliation":[{"name":"University of Iowa Hospitals and Clinics, Iowa City, lowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Glaspy","sequence":"additional","affiliation":[{"name":"University of California Los Angeles School of Medicine, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Hamid","sequence":"additional","affiliation":[{"name":"The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrick","family":"Ross","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Friedlander","sequence":"additional","affiliation":[{"name":"Mount Sinai School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Garbe","sequence":"additional","affiliation":[{"name":"University Hospital Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Logan","sequence":"additional","affiliation":[{"name":"Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Hauschild","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Lebb\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris AP-HP Dermatology CIC Departments, H\u00f4pital Saint-Louis, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshada","family":"Joshi","sequence":"additional","affiliation":[{"name":"Parexel, Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Snyder","sequence":"additional","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M","family":"Mehnert","sequence":"additional","affiliation":[{"name":"Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"2025100305141992000_11.5.e006270.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414428"},{"key":"2025100305141992000_11.5.e006270.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"2025100305141992000_11.5.e006270.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30142-6"},{"key":"2025100305141992000_11.5.e006270.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408868"},{"key":"2025100305141992000_11.5.e006270.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406037"},{"key":"2025100305141992000_11.5.e006270.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412690"},{"key":"2025100305141992000_11.5.e006270.7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2667"},{"key":"2025100305141992000_11.5.e006270.8","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.3377"},{"key":"2025100305141992000_11.5.e006270.9","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-019-0623-z","article-title":"Final 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