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Aviscumine (ME-503)-Skin Reaction as significant Factor for its Efficacy Expanded Evaluation of the Results from the Phase II Trial NCT00658437 in Patients with Unresectable stage IV Metastatic Melanoma

Uwe Trefzer, Ralf Gutzmer, Tabea Wilhelm, Florian Schenck, Katharina C. Kähler, Volkmar Jacobi, Klaus Witthohn, Hans Lentzen* and Peter Mohr

Aviscumine (ME-503), a recombinant lectin, enhances inflammatory cytokine (esp. IL-1β) release, activation of Langerhans cells, and T-cell responses. An extended evaluation of phase II data of the patient cohorts with/without skin reactions within the first treatment cycle after SC injection regarding the efficacy of aviscumine are presented. 31 patients (ITT total population) (ECOG: 0 or 1) with progressive stage IV malignant melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial (NCT00658437). Patients received 350 ng aviscumine twice weekly by SC injection until progression. Tumor response was assessed every eight weeks, survival of patients was followed up to one year after the end of therapy. 21 patients with skin reactions vs. 9 patients without skin reactions as adverse events were assessed for efficacy in an expanded evaluation.

Comparing the median overall survival data (mOS) in patients (n=9) without injection site reactions (mOS: 5.1 months; 95% CI 2.1-6.9; 1-year survival rate: 0%) with survival data in patients (n=21) showing injection site reactions (mOS: 14.6 months; 95% CI 11.0-19.8; 1-year survival rate: 62%) a clear difference in favor of the patients with skin reactions is seen. The difference in overall survival between these two groups of patients was high significant (p<0.0001). In the total ITT population (n=31) the mOS was 11.0 months (95% CI 6.9-19.8) and the 1- year survival rate was 45%.

Preliminary conclusions from our small cohorts suggest a strong clinical impact of aviscumine in patients with previously treated metastatic melanoma if those patients show injection site reactions as adverse events after SC injection within the first treatment cycle. Patients without any injection site reactions apparently failed to prove clinical benefit.