Abstract CT123: Aviscumine (ME-503), a plant protein with a novel mode of action, shows clinical activity in unresectable stage IV metastatic melanoma: data from a phase II trial
Authors: Mohr Peter , Trefzer Uwe , Gutzmer Ralf , Wilhelm Tabea , Schenck Florian , Kähler Katharina C. , Jacobi Volkmar , Witthohn Klaus , Lentzen Hans 
Published: July 2016

Abstract
Background: Aviscumine, a recombinant protein, inactivates the 28S rRNA (“ribotoxic stress”) after endocytosis and enhances inflammatory cytokine (esp. IL-1ß) release, activation of Langerhans cells and T-cell responses. Phase II data of the total patient population vs. a small patient cohort with/without skin reactions after SC injection are reported regarding the efficacy of aviscumine in patients with progressive metastatic melanoma stage IV.
Methods: 32 pts. (ECOG: 0 or 1) 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. 30 patients were assessed for overall survival (OS) and skin reactions were monitored as adverse events.
Results: The median OS of the 30 patients was 10.7 months; (95% CI 6.4-14.3). The patients had a 1-year survival rate of 43.3%. The patients with an injection side reaction (n = 21) during the first cycle of treatment showed a mOS of 14.6 months (95% CI 11.0 - 19.8) whereas the survival data in patients (n = 9) without injection site reactions were 5.1 months (95% CI 2.1-6.9). No patient in this group without skin reactions survived 1-year. Comparing the 2 groups with / without skin reactions a clear difference in favor of the patients with injection site reactions is seen. High significance (p&lt;0.0001) was obtained. An advantage in mOS of patients with skin reactions was observed in all subgroups of the trial.
Conclusion: These results suggest a strong clinical impact of aviscumine in patients with previously treated metastatic melanoma if those patients show injection site reactions as a sign of an immune reaction after SC injection within the first treatment cycle. Patients without any injection site reactions apparently failed to prove clinical benefit. Due to relatively small sample size in this study, these findings require validation in a larger patient cohort. “skin reaction” populationtotal populationmOS (months) (95% CI)1-y-OS (%)nmOS (months) (95% CI)1-y-OS (%)nOverall14.6 (11.0-19.8)62.02110.7 (6.4-14.3)43.330Female14.5 (11.3-15.3)66.71213.9 (10.3-15.2)53.315Male12.4 (8.7-14.6)55.696.3 (2.6-12.4)33.315ECOG 014.3 (8.7-15.3)53.81310.4 (6.4-14.8)41.217ECOG 114.1 (11.0-15.5)75.0811.0 (5.1-14.2)46.213M1c14.1 (8.9-15.2)57.1148.8 (6.3-14.2)36.422≤ 60 yrs11.3 (8.7-15.5)33.369.9 (6.4-14.6)25.08&gt; 60 yrs14.3 (10.4-15.3)73.31511.4 (5.2-14.8)50.022&lt;= 1 pre-treatment14.4 (11.3-15.3)70.01011.3 (6.9-14.8)46.715&gt; 1 pre-treatment14.3 (8.7-15.3)54.5118.9 (5.1-14.3)40.015
Citation Format: Peter Mohr, Uwe Trefzer, Ralf Gutzmer, Tabea Wilhelm, Florian Schenck, Katharina C. Kähler, Volkmar Jacobi, Klaus Witthohn, Hans Lentzen. Aviscumine (ME-503), a plant protein with a novel mode of action, shows clinical activity in unresectable stage IV metastatic melanoma: data from a phase II trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT123.