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@ARTICLE{Khler:302826,
      author       = {K. C. Kähler and J. C. Hassel and M. Ziemer and P.
                      Rutkowski and F. Meier and L. Flatz and C. Gaudy-Marqueste
                      and L. Zimmer$^*$ and M. Santinami and F. Russano and I. von
                      Wasielewski and T. K. Eigentler and M. Maio and I. Zalaudek
                      and S. Haferkamp and P. Quaglino and J. Welzel and C.
                      Röcken and A. Enk and J.-C. Simon and T. Świtaj and M.
                      Garzarolli and T. Amaral and N. Malissen and E.
                      Livingstone$^*$ and G. Elia and A. Covelli and K. Lorizzo
                      and D. Neri and S. Mulatto and A. Parca and B. Pizzichi and
                      P. A. Ascierto and C. Garbe and C. Robert and D.
                      Schadendorf$^*$ and A. Hauschild},
      title        = {{N}eoadjuvant {I}ntralesional {T}argeted {I}mmunocytokines
                      ({D}aromun) in {S}tage {III} {M}elanoma.},
      journal      = {Annals of oncology},
      volume       = {nn},
      issn         = {0923-7534},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-01366},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {This phase 3 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 (AJCC version 7).Patients
                      were randomized to 4 weekly intralesional daromun
                      administrations (13 Mio IU of L19IL2 and 400 μg of L19TNF)
                      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.246 patients were randomized and included in
                      the intention-to-treat analysis: $74\%$ had undergone ≥ 2
                      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 and 6.8 months, respectively (HR 0.59; $95\%$ CI 0.41
                      to 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.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.},
      keywords     = {Neoadjuvant (Other) / immunotherapy (Other) / intralesional
                      (Other) / locally advanced (Other) / melanoma (Other) /
                      resectable (Other) / targeted immunocytokines (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40633690},
      doi          = {10.1016/j.annonc.2025.06.014},
      url          = {https://inrepo02.dkfz.de/record/302826},
}