9028 Background: Aflibercept is a fusion protein combining the Fc portion of human IgG1with the extracellular ligand-binding domains of human VEGFR1 and VEGFR2, acting as a high-affinity soluble VEGF receptor and potent angiogenesis inhibitor. Methods: Phase II study of aflibercept in patients with inoperable stage III or IV melanoma who had received no prior chemotherapy or hormonal therapy. A 2-stage design was adopted focusing upon response rate (RECIST) and 4-month PFS rate. First stage accrual of 21 patients was specified, while final accrual of 41 is planned, with adequate response/4 month PFSR. Aflibercept was given at 4 mg/kg IV every 2 weeks. Response was assessed every 8 weeks. Results: Twenty seven patients (16 male, 11 female), age 23–83 (median 58) have been enrolled to date. All had AJCC stage IV melanoma (3M1a, 3M1b, 21M1c). Karnofsky PS: 100 (13), 90 (11) or 80 (3). Nine patients had primary ocular melanoma, 16 cutaneous and 2 unknown primary site. A total of 160 cycles have been administered (median 4; range 1–18). Grade 3/4 toxicities included cerebral ischemia (1 patient; 4%), confusion (1; 4%), thrombocytopenia (1; 4%), hypertension (7; 26%), hypotension (1; 4%), left ventricular diastolic dysfunction (1; 4%), fatigue (1; 4%), proteinuria (4; 15%), extraocular muscle paresis (1; 4%), renal failure (1; 4%), back pain (1; 4%), headache (1; 4%). Interim analysis was conducted after the first 21 patients (stage 1). Eight (1 M1a, 1M1b, 6M1c; 4 ocular, 3 cutaneous, 1 unknown primary) of the first 21 patients had at least 4 months of PFS (10 out of 27; 2 additional patients with cutaneous melanoma had SD: 1M1a and 1M1c). One patient (23rd; cutaneous, M1c) had a confirmed complete remission. Four patients were taken off study prior to response evaluation for toxicity (3) or treatment refusal (1). One patient is currently disease free who was not evaluable for response (previous surgery and radiofrequency ablation of measurable disease site). Eleven patients had progression. Conclusions: Aflibercept can be administered with acceptable toxicity, and exhibits promising antitumor efficacy against advanced melanoma. This study continues second stage accrual with anticipated closure before June 2009. [Table: see text]
Randomized Phase II Study of IL-2 With or Without an Allogeneic Large Multivalent Immunogen Vaccine for the Treatment of Stage IV Melanoma