Kahler, K. C. and Hassel, J. C. and Ziemer, M. and Rutkowski, P. and Meier, F. and Flatz, L. and Gaudy-Marqueste, C. and Zimmer, L. and Santinami, M. and Russano, F. and von Wasielewski, I. and Eigentler, T. K. and Maio, M. and Zalaudek, I. and Haferkamp, Sebastian and Quaglino, P. and Welzel, J. and Rocken, C. and Enk, A. and Simon, C. and Switaj, T. and Garzarolli, M. and Amaral, T. and Malissen, N. and Livingstone, E. and Elia, G. and Covelli, A. and Lorizzo, K. and Neri, D. and Mulatto, S. and Parca, A. and Pizzichi, B. and Ascierto, P. A. and Garbe, C. and Robert, C. and Schadendorf, D. and Hauschild, A. (2025) Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma. ANNALS OF ONCOLOGY, 36 (10). ISSN 0923-7534, 1569-8041
Full text not available from this repository. (Request a copy)Abstract
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 Patients and methods: Patients were randomized to weekly intralesional daromun administrations (13 million IU of L19IL2 and 400 mu g 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 Type: | Article |
|---|---|
| Uncontrolled Keywords: | FIBRONECTIN ISOFORM; COMBINATION; DACARBAZINE; THERAPY; neoadjuvant; melanoma; resectable; locally advanced; targeted immunocytokines; immunotherapy; intralesional |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2026 05:43 |
| Last Modified: | 27 Mar 2026 05:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67968 |
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