title: Clinical and pharmacologic evaluation of two dose levels of intetumumab (CNTO 95) in patients with melanoma or angiosarcoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: The Angeles Clinic and Research Institute, 2001 Santa Monica Boulevard, Suite 560W, Santa Monica, CA 90404, USA. SOday@TheAngelesClinic.org
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'Day
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Mark R
authors.initials: MR
authors.lastname: Albertini
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Heidi
authors.initials: H
authors.lastname: Schalch
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Lang
authors.forename: Jie
authors.initials: J
authors.lastname: Ling
authors.forename: Marielena
authors.initials: M
authors.lastname: Mata
authors.forename: Manjula
authors.initials: M
authors.lastname: Reddy
authors.forename: Brenda
authors.initials: B
authors.lastname: Foster
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006394:Hemangiosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000097:blood; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016023:Integrins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C486839:intetumumab