{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:11:28Z","timestamp":1792008688215,"version":"4.4.0"},"reference-count":5,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Daromun (L19IL2\/L19TNF) was investigated as a neoadjuvant, intralesional therapy for patients with fully resectable stage III melanoma in the phase III PIVOTAL trial (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT02938299\">NCT02938299<\/jats:ext-link>\n                      ). The trial enrolled 256 patients in the European Union and met its primary end point, demonstrating a statistically significant improvement in recurrence-free survival (RFS; hazard ratio, 0.59;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .005) for daromun followed by surgery versus up-front surgery, at a median follow-up (FU) of 21 months from random assignment. PIVOTAL included two clinically distinct subgroups, namely, patients with de novo diagnosed metastatic disease (n = 34; 13%) and patients with recurrence(s) after surgery with or without radiotherapy and\/or adjuvant systemic therapies (n = 222; 87%). Here, we present an updated analysis of the primary and secondary end points, including safety data, at a median FU of 36.8 months from random assignment (database cutoff: November 28, 2025), alongside new sensitivity analyses of event-free survival (EFS). The updated analysis confirms the clinically and statistically meaningful improvements in RFS and distant metastasis-free survival recorded in the neoadjuvant daromun versus control arm. The EFS post hoc analysis, conducted in both the overall population and the recurrent patient subgroups (with or without prior systemic therapies), provides consistency and robustness to the benefit of neoadjuvant daromun observed for the primary efficacy end point. No new safety signals of concern were recorded.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00852","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:00:07Z","timestamp":1786478407000},"page":"2662-2669","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Neoadjuvant Intralesional Daromun (L19IL2\/L19TNF) in Resectable Locally Advanced Melanoma: An Update on the Efficacy and Safety Results of the PIVOTAL Phase III Trial"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1212-9587","authenticated-orcid":false,"given":"Axel","family":"Hauschild","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-6230","authenticated-orcid":false,"given":"Jessica Cecile","family":"Hassel","sequence":"additional","affiliation":[{"name":"Department of Dermatology and NCT, Heidelberg University, Medical Faculty, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjana","family":"Ziemer","sequence":"additional","affiliation":[{"name":"Skin Cancer Center, University Hospital Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8920-5429","authenticated-orcid":false,"given":"Piotr","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Department of Soft Tissue\/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-9706","authenticated-orcid":false,"given":"Friedegund","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-8390","authenticated-orcid":false,"given":"Lukas","family":"Flatz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Center for Dermatooncology, Eberhard Karls University of Tu\u0308bingen, Tu\u0308bingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gaudy-Marqueste","sequence":"additional","affiliation":[{"name":"Dermatology and Skin Cancer Department, Aix-Marseille University, Assistance Publique-H\u00f4pitaux de Marseille, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8436-4757","authenticated-orcid":false,"given":"Mario","family":"Santinami","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4616-7753","authenticated-orcid":false,"given":"Francesco","family":"Russano","sequence":"additional","affiliation":[{"name":"IOV\u2014Istituto Oncologico Veneto\u2014IRCCS, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke","family":"von Wasielewski","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Eigentler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology, Charit\u00e9-Universitaetsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-6321","authenticated-orcid":false,"given":"Michele","family":"Maio","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, University Hospital of Siena, NIBIT Foundation Onlus, University of Siena, Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7878-4955","authenticated-orcid":false,"given":"Iris","family":"Zalaudek","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology of the Medical University of Triest, Trieste, Italy"},{"name":"Department of Dermatology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-8345","authenticated-orcid":false,"given":"Sebastian","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital of Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Quaglino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Welzel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Augsburg, Comprehensive Cancer Center Augsburg, BZKF Bavarian Center for Cancer Research, Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-4961","authenticated-orcid":false,"given":"Michael","family":"Weichenthal","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliano","family":"Elia","sequence":"additional","affiliation":[{"name":"Philochem AG, Otelfingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Covelli","sequence":"additional","affiliation":[{"name":"Philogen S.p.A., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Lorizzo","sequence":"additional","affiliation":[{"name":"Philogen S.p.A., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Parca","sequence":"additional","affiliation":[{"name":"Philogen S.p.A., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Neri","sequence":"additional","affiliation":[{"name":"Philogen S.p.A., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo Antonio","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d and Istituto Nazionale Tumori IRCCS Fondazione \u201cG. Pascale\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-0238","authenticated-orcid":false,"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"Institute Gustave Roussy, Villejuif-Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-7858","authenticated-orcid":false,"given":"Dirk","family":"Schadendorf","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center (Westdeutsches Tumorzentrum), University Hospital Essen, German Cancer Consortium (DKTK)-Heidelberg, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina Charlotte","family":"Kaehler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2402604"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211437"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-016-1952-0"},{"key":"e_1_3_9_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-015-1704-6"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.06.014"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-26-00852","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:59:23Z","timestamp":1790632763000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-26-00852"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":5,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1200\/JCO-26-00852"],"URL":"https:\/\/doi.org\/10.1200\/jco-26-00852","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"assertion":[{"value":"2026-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-09","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}