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Publications

Journal Article Ahead of print 2 citations

PubMed: 42579833 DOI: 10.1200/JCO-26-00852

Neoadjuvant Intralesional Daromun (L19IL2/L19TNF) in Resectable Locally Advanced Melanoma: An Update on the Efficacy and Safety Results of the PIVOTAL Phase III Trial.

J Clin Oncol

Authors: Axel Hauschild, Jessica Cecile Hassel, Mirjana Ziemer, Piotr Rutkowski, Friedegund Meier, Lukas Flatz, Caroline Gaudy-Marqueste, Mario Santinami, Francesco Russano, Imke von Wasielewski, Thomas Eigentler, Michele Maio, Iris Zalaudek, Sebastian Haferkamp, Pietro Quaglino, Julia Welzel, Michael Weichenthal, Giuliano Elia, Alfredo Covelli, Katia Lorizzo, Agnese Parca, Dario Neri, Paolo Antonio Ascierto, Caroline Robert, Dirk Schadendorf, Katharina Charlotte Kaehler

Affiliations

  • Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany.
  • Department of Dermatology and NCT, Heidelberg University, Medical Faculty, University Hospital Heidelberg, Heidelberg, Germany.
  • Skin Cancer Center, University Hospital Leipzig, Leipzig, Germany.
  • Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
  • Department of Dermatology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
  • Department of Dermatology, Center for Dermatooncology, Eberhard Karls University of Tübingen, Tübingen, Germany.
  • Dermatology and Skin Cancer Department, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • IOV-Istituto Oncologico Veneto-IRCCS, Padua, Italy.
  • Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany.
  • Department of Dermatology, Venerology and Allergology, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
  • Center for Immuno-Oncology, University Hospital of Siena, NIBIT Foundation Onlus, University of Siena, Siena, Italy.
  • Department of Dermatology and Venereology of the Medical University of Triest, Trieste, Italy.
  • Department of Dermatology, Medical University of Graz, Graz, Austria.
  • Department of Dermatology, University Hospital of Regensburg, Regensburg, Germany.
  • Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy.
  • Department of Dermatology, University Hospital Augsburg, Comprehensive Cancer Center Augsburg, BZKF Bavarian Center for Cancer Research, Augsburg, Germany.
  • Philochem AG, Otelfingen, Switzerland.
  • Philogen S.p.A. Siena, Italy.
  • Università degli Studi di Napoli "Federico II" and Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", Naples, Italy.
  • Institute Gustave Roussy, Villejuif-Paris, France.
  • Comprehensive Cancer Center (Westdeutsches Tumorzentrum), University Hospital Essen, German Cancer Consortium (DKTK)-Heidelberg, Essen, Germany.

Abstract

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: NCT02938299). 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; P = .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.

MeSH

Safety, Melanoma, Therapeutics