e19015 Background: CY-503 is a recombinant mistletoe lectin ( INN: aviscumine) leading to catalytical inactivation of ribosomes, thereby inhibiting protein synthesis. Dependent on dosage immunomodulatory and cytotoxic effects are induced. In patients (pts.) with stage IV metastatic melanoma CY-503 could potentially lead to an antitumoral response. Methods: Pts. with stage IV metastatic melanoma (ECOG performance score 0-1), who had failed from one or more previous systemic chemotherapies, were eligible in this trial. Pts. with severe organ dysfunction or brain metastasis were excluded. Pts. received CY-503 350ng SC twice weekly for a minimum of 8 weeks (2 cycles). Pts. without disease progression were continued. The primary study endpoints were progression free survival (PFS) and overall survival (OS). Tumor assessment included CT and MRI scans every 8 weeks, which were centrally reviewed. Results: Between April 2008 and June 2009, 32 pts. were enrolled, one being ineligible. 31 pts. (16m; 15f) with a median age of 67 years (range: 20-85y) were evaluable. Pts. were belonging to the following stage IV categories: M1a/b/c = 4/5/22, and median number of prior treatments was 2 (range: 1- 6), 7 pts. (23%) were pretreated with ≥ 3 lines. (84%) received at least 8 weeks of treatment; 4 pts. withdrew prior to 8 weeks due to clinically overt disease progression, and 1 pt. due to a severe adverse event (SAE). At 8 weeks 11 pts. with stable disease (SD) were observed (disease control rate: 36% ITT) with a median PFS of 3.75 months (95% CI: 3,6-3,9 months). The median PFS in the ITT population was 2.0 months (95% CI: 1.9–2.1 months). Median OS had not been reached at the time of evaluation. Local reactions at the injection site were the main toxicities. Two severe adverse events with fatal outcome (1 pt. with cardiac arrhythmia, 1 pt. with stroke) could not clearly be related to the study medication. Conclusions: CY-503 showed a modest clinical activity in pts. with advanced melanoma. Side effects were mostly limited to local reactions at injection site. Given this heavily pretreated population, further investigations on the use of CY-503 in the treatment of malignant melanoma might be warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytavis Biopharm GmbH Cytavis Biopharm GmbH Cytavis Biopharm GmbH Cytavis Biopharm GmbH