Abstract
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.
Highlights
Aviscumine (ME-503; formerly CY-503) is a class class II ribosome-inactivating protein (II) ribosomeinactivating protein (RIP II) with immune modulatory properties including activation of natural killer cells, and antigen-presenting cells, induction of T-cell responses, and stimulation of proinflammatory cytokine release
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)
In this paper we present an extended evaluation of the phase II data regarding the efficacy of the immune modulator aviscumine in the total patient population vs. patient cohorts with/without skin reactions after SC injection
Summary
Aviscumine (ME-503; formerly CY-503) is a class II ribosomeinactivating protein (RIP II) with immune modulatory properties including activation of natural killer cells, and antigen-presenting cells, induction of T-cell responses, and stimulation of proinflammatory cytokine release After internalisation into the target cell (e.g. monocytes/macrophages, dendritic cells), and subsequent cleavage of the N-glycosidic bond of the adenine-4324 residue in the eukaryotic 28S ribosomal RNA the holoprotein induces catalytic inactivation of the ribosomes and inhibition of protein synthesis („ribotoxic stress“) [3]. The holoprotein induces a priming signal that results in the transcription of pro-IL-1β and pro-IL-18 in macrophages/monocytes, (immature) dendritic cells, Kupffer cells, keratinocytes, chondrocytes, epithelial cells. IL-1β release is due to the activity of caspase-1 (interleukin 1 converting enzyme), a scaffolding complex that mediates pro-IL-1β cleavage to active IL-1β. This mode of action of aviscumine is characteristic for RIP II [4,5]
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