A randomized phase II study of EMD 121974 in patients (pts) with metastatic melanoma (MM)

8548 Background: EMD 121974 is a selective antagonist of avβ3 integrin, which promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells expressing avβ3 integrin. We conducted a randomized phase II trial of cilengitide in pts with MM to evaluate the clinical efficacy at 2 different doses. Methods: Pts with stage IV or unresectable stage III non-choroidal melanoma who had no more than 1 prior systemic therapy were enrolled. Pts at least 18 years of age and with ECOG performance status of 0 to 2 were eligible. All pts underwent baseline tumor biopsy and were randomly assigned to either 500 mg or 2,000 mg intravenous (IV) EMD 121974 twice weekly, using the following stratification factors: 1) prior systemic treatment; 2) visceral metastases; 3) serum lactate dehydrogenase level; 4) tumor avβ3 overexpression, where overexpression is defined as > 25% of melanoma cells staining positive. The primary objective of this study was to determine the progression-free survival rate at 8 weeks. Results: Twenty-nine pts were enrolled, and 26 pts (14 at 500 mg; 12 at 2,000 mg dose) were treated. Patient characteristics for 500 mg and 2,000 mg arm, respectively, are as follows: median age, 57 and 61; percentage (% age) of male, 50% and 50%; % age of ECOG performance status of 0, 79% and 58%; % age of stage IV, 79% and 75%; % age of tumor avβ3 overexpression, 21% and 25%. Three of 26 pts were progression-free at 8 weeks (2 at 500 mg; 1 at 2,000 mg dose). One pt at 2,000 mg had a prolonged partial response after initial 28% enlargement of target lesions. There were no grade 3 or 4 adverse events (AEs) except one pt with grade 3 lymphopenia at 2,000 mg. Although both doses of EMD 121974 were well tolerated, the 2,000 mg was associated with higher incidences of grade 2 fatigue, arthralgia, lymphopenia, peripheral neuropathy, and GI AEs. Optional tumor biopsies were performed on day 8, and the correlative studies to examine the molecular changes in the tumor are currently in progress. Conclusions: IV EMD 121974, 500 or 2,000 mg twice weekly, was well tolerated but had minimal clinical efficacy as a single-agent for MM. Supported by NCI grant N01 CM-17003 and CA16672 No significant financial relationships to disclose.