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A phase II, randomized, open-label study evaluating the antitumor activity of MEDI-522, a humanized monoclonal antibody directed against the human alpha v beta 3 (avb3) integrin, ± dacarbazine (DTIC) in patients with metastatic melanoma (MM)
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2005
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ImmunologyImmunotherapeuticsImmunotherapyHumanized Monoclonal AntibodyOncologyTumor ImmunityAnti-cancer AgentCancer ResearchMolecular OncologyCancer GrowthTumor GrowthMelanomaMedi-522 ± DticMetastatic MelanomaImmune SurveillanceCancer TreatmentPharmacologyStage Iv MmMedicinePhase Ii
7507 Background: MEDI-522 targets integrin avb3, which plays a critical role in angiogenesis, bone resorption, tumor growth and metastasis and is highly expressed in MM. Methods: This multicenter, non-comparative study explored the antitumor activity and safety of MEDI-522 (8 mg/kg/week) with or without DTIC (1000 mg/m2 once every 3 weeks) in patients (pts) with Stage IV MM. Eligibility included ECOG 0/1 and no prior therapy for MM except adjuvant immunotherapy. Treatment was until disease progression, unacceptable toxicity, or other reasons for pt withdrawal, or until the end of the study. Tumor was assessed after every 2 treatment cycles. Antitumor endpoints were objective response rate (ORR), early disease progression rate (EDPR) at first tumor assessment, progression-free survival (PFS), and overall survival (OS). Stratification was by site of distant metastasis. Results: 112 patients (57 to MEDI-522 [Arm 1] and 55 to MEDI-522 + DTIC [Arm 2]) were randomized between 09/03–05/04. Median age was 59 years, M/F (68%/32%), ECOG 0/1 (79%/21%), and Stage IV M1a/M1b/M1c (10%/30%/60%). Most adverse events (AEs) were Grade 1/2. Grade ≥3 AEs occurred in 21 (37%) pts in Arm 1 and 26 (48%) pts in Arm 2. MEDI-522-related deaths (myocardial infarction and pulmonary embolism) occurred in 2 pts, 1 pt in each arm. Most common Grade 3/4 AEs in Arm 2 were hematologic (17% neutropenia, 9% thrombocytopenia, and 6% each for anemia/leukopenia). 1 (2%) pt in Arm 1 had Grade 3 thrombocytopenia. Arm 1: ORR was 0%, EDPR was 49%, and median PFS was 1.4 months. Arm 2: ORR was 13%, EDPR was 38%, and median PFS was 2.6 months. Based on ongoing follow-up, approximately 70% of pts are alive at 6 months in each arm; median follow-up is 8 months. Conclusions: MEDI-522 with or without DTIC appears well tolerated. The preliminary OS results in both arms suggest potential clinical activity of MEDI-522 ± DTIC in MM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune Chiron, MedImmune MedImmune (clinical trial - research contract; not to myself)