Purpose In this Phase 1, multicenter, open-label study, intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody was evaluated for safety, pharmacokinetics, and pharmacodynamic activity in patients with melanoma or angiosarcoma. Patients and methods Patients with histologically-confirmed inoperable melanoma or angiosarcoma refractory to standard treatment were allocated to treatment with 10 mg/kg or 20 mg/kg intetumumab, administered once every 3 weeks for up to four cycles unless unacceptable toxicity or disease progression occurred. Extended dosing was available for patients who responded with stable disease or better. Results Eight patients received 10 mg/kg and 11 received 20 mg/kg intetumumab. Baseline patient characteristics were comparable between treatment groups; 18 patients had metastatic malignant melanoma and one had angiosarcoma. No dose-limiting toxicities were observed. Headache was the most common adverse event across both dose groups. Vomiting, nausea and chills were more common, and uveitic reactions lasted longer, in patients treated with 20 mg/kg compared with 10 mg/kg intetumumab. No patient developed antibodies to intetumumab. Intetumumab drug exposure as assessed by area under the curve and maximum serum concentration appeared to increase approximately dose-proportionally from 10 to 20 mg/kg, while volume of distribution remained constant for both doses. Stable disease was observed in two patients with metastatic malignant melanoma (one in each dose group) for at least 6 weeks. Conclusions In patients with metastatic malignant melanoma and angiosarcoma in this study, intetumumab demonstrated manageable toxicity, was well tolerated, and presented approximately dose-proportional pharmacokinetics for the 10 mg/kg and 20 mg/kg doses.