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Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma

Background - This phase III trial assessed daromun, a combination of two fibronectin-targeting immunocytokines (L19IL2 and L19TNF), as a neoadjuvant treatment for patients with clinically detectable stage IIIB/C melanoma [American Joint Committee on Cancer (AJCC) version 7]. - Patients and methods -...

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Main Authors: Kähler, Katharina C. (Author) , Hassel, Jessica C. (Author) , Ziemer, M. (Author) , Rutkowski, P. (Author) , Meier, F. (Author) , Flatz, L. (Author) , Gaudy-Marqueste, C. (Author) , Zimmer, L. (Author) , Santinami, M. (Author) , Russano, F. (Author) , von Wasielewski, I. (Author) , Eigentler, T. K. (Author) , Maio, M. (Author) , Zalaudek, I. (Author) , Haferkamp, S. (Author) , Quaglino, P. (Author) , Welzel, J. (Author) , Röcken, C. (Author) , Enk, A. (Author) , Simon, J. -C. (Author) , Świtaj, T. (Author) , Garzarolli, M. (Author) , Amaral, T. (Author) , Malissen, N. (Author) , Livingstone, E. (Author) , Elia, G. (Author) , Covelli, A. (Author) , Lorizzo, K. (Author) , Neri, D. (Author) , Mulatto, S. (Author) , Parca, A. (Author) , Pizzichi, B. (Author) , Ascierto, P. A. (Author) , Garbe, C. (Author) , Robert, C. (Author) , Schadendorf, D. (Author) , Hauschild, Axel (Author)
Format: Article (Journal)
Language:English
Published: 7 July 2025
In: Annals of oncology
Year: 2025, Volume: 36, Issue: 10, Pages: 1166-1177
ISSN:1569-8041
DOI:10.1016/j.annonc.2025.06.014
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.annonc.2025.06.014
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0923753425008294
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Author Notes:K.C. Kähler, J.C. Hassel, M. Ziemer, P. Rutkowski, F. Meier, L. Flatz, C. Gaudy-Marqueste, L. Zimmer, M. Santinami, F. Russano, I. von Wasielewski, T.K. Eigentler, M. Maio, I. Zalaudek, S. Haferkamp, P. Quaglino, J. Welzel, C. Röcken, A. Enk, J. -C. Simon, T. Świtaj, M. Garzarolli, T. Amaral, N. Malissen, E. Livingstone, G. Elia, A. Covelli, K. Lorizzo, D. Neri, S. Mulatto, A. Parca, B. Pizzichi, P.A. Ascierto, C. Garbe, C. Robert, D. Schadendorf & A. Hauschild
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Summary:Background - This phase III trial assessed daromun, a combination of two fibronectin-targeting immunocytokines (L19IL2 and L19TNF), as a neoadjuvant treatment for patients with clinically detectable stage IIIB/C melanoma [American Joint Committee on Cancer (AJCC) version 7]. - Patients and methods - Patients were randomized to weekly intralesional daromun administrations (13 million IU of L19IL2 and 400 μg of L19TNF) for 4 weeks followed by surgery, or upfront surgery. Pretreatment with approved adjuvant agents was allowed. The primary endpoint was recurrence-free survival (RFS): events were disease recurrence or death from any cause after complete surgical tumor resection (ClinicalTrials.gov NCT02938299). - Results - A total of 246 patients were randomized and included in the intention-to-treat analysis: 74% had undergone two or more prior surgical resections and 35% had received prior systemic therapy. At a median follow-up of 21 months, the neoadjuvant group (n = 122) had a significantly longer RFS than the upfront surgery group (n = 124), with a median RFS of 16.7 months and 6.8 months, respectively [hazard ratio (HR) 0.59, 95% confidence interval (CI 0.41-0.86), P = 0.005, log-rank test]. The risk of distant recurrence was reduced by 40% in the neoadjuvant arm (HR 0.60, 95% CI 0.37-0.95, P = 0.029). Grade ≥3 treatment-related adverse events (TRAEs) were 6.7% in the surgery-alone arm and 27.1% in the daromun arm, mostly injection site reactions. - Conclusions - Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma. TRAEs were transient and manageable. Neoadjuvant daromun is a new therapeutic option for patients with stage III melanoma, including those with locoregional recurrence after surgery and previous adjuvant therapy.
Item Description:Gesehen am 09.04.2026
Physical Description:Online Resource
ISSN:1569-8041
DOI:10.1016/j.annonc.2025.06.014

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