Malignant Melanoma, Skin Clinical Trial
Official title:
A Phase II Study of Intratumoral Application of L19IL2/L19TNF in Melanoma Patients in Clinical Stage III or Stage IV M1a With Presence of Injectable Cutaneous and/or Subcutaneous Lesions
This Phase II study is an uncontrolled, multicenter, prospective study for patients with
malignant melanoma of the skin in clinical stage III or stage IV M1a.
Twenty Patients will be treated with a mixture of L19IL2 and L19TNF once weekly for up to 4
weeks.
The dose will be distributed among the lesions via multiple intralesional injections.
The proportion of patients with complete response at week 12 will be calculated.
L19IL2 is a recombinant fusion protein composed of a fully human recombinant monoclonal
antibody (L19) and the human recombinant interleukin-2 (IL-2).
IL2, is a potent stimulator of the immune response. It has a central role in the regulation
of T cell responses and effects on other immune cells such as natural killer cells, B cells,
monocyte/macrophages and neutrophils. IL2 can induce tumor regression through its ability to
stimulate a potent cell-mediated immune response in vivo.
L19TNF is a recombinant fusion protein composed of a fully human recombinant monoclonal
antibody (L19) and the human tumor necrosis factor-alpha, a primary mediator of immune
regulation and inflammation.
As an anti-tumor agent, TNF exerts its major effects via a preferential toxicity for the
endothelial cells of the tumor-associated vasculature and an increase of the antitumor
immune response. Given at sufficient doses (e.g. intratumorally or in the ILP setting with
melphalan), TNF causes significant tumor shrinkage in solid cancer subjects.
This phase II signal generating study is designed to test the efficacy and safety of an
intratumorally administered mixture of L19IL2 + L19TNF in patients suffering from metastatic
melanoma. It is well documented that the intratumoral administration of IL-2 leads to a high
response rate and unexpectedly favorable longtime outcome and several tumor responses have
been observed in clinical trials of Philogen, both using intratumorally administered L19IL2
and L19TNF in the ILP setting.
Preclinical data produced within the Philogen group now suggest that the intratumoral
administration of a mixture of L19IL2 and L19TNF could be even more effective. After only
one intratumoral administration of a mixture of L19IL2 and L19TNF tumors disappeared
completely while neither L19IL2 nor L19TNF monotherapy was nearly as effective.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment