Despite recent advances in therapeutic options for advanced Melanoma patients, there is still an unmet medical need for Melanoma patients with local recurrence (Stage III), who are candidates for surgical resection of all metastases. This category of patients is at a high risk of further recurrences until the disease becomes inoperable (unresectable) or progresses to Stage IV (distant organ involvement), for which the prognosis is particularly grim.
Daromun is a combination of the immunocytokines L19-IL2 (Darleukin) and L19-TNF (Fibromun), which is being developed as neoadjuvant intralesional treatment for Stage III B and C melanoma patients.
In animal models of tumor, including melanoma, the combination has shown strong synergistic effects, dependent on T cell activity, and a clear superiority to each individual immunocytokine used as a single agent in achieving cure of animals.
Aimed at blocking or delaying progression of the disease to stage IV, a Phase II study of intralesional treatment with Daromun in stage III/IVA Melanoma patients (i) showed efficacy in terms of complete and partial response of the injected metastases, (ii) led to a systemic immune response, i.e. non-injected lesions (neighboring or distant) shrank or disappeared upon intralesional injection (bystander effect), (iii) and recorded a decelerated progression to stage IV melanoma of treated patients with respect to historical controls (EudraCT No. 2012-001991-13).
Two randomized, controlled Phase III registration trials for intralesional application of Daromun as a neoadjuvant, followed by surgery and compared to surgery alone (standard of care) are presently ongoing in Europe and in the USA in patients with fully resectable stage IIIB/C Melanoma. The primary endpoint is recurrence-free survival, with overall survival as key secondary endpoint.
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