title: A randomised, phase II study of intetumumab, an anti-αv-integrin mAb, alone and with dacarbazine in stage IV melanoma.
abstract: BACKGROUND
  α(v) integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-α(v)-integrin monoclonal antibody.
  
  
  METHODS
  In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics.
  
  
  RESULTS
  No statistically significant differences in efficacy were observed between groups. In the dacarbazine+placebo, dacarbazine+intetumumab, 10 mg kg(-1) intetumumab, and 5 mg kg(-1) intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of complete+partial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred.
  
  
  CONCLUSIONS
  With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma.
authors.affiliation: The Angeles Clinic and Research Institute, 2001 Santa Monica Boulevard, Suite 560W, Santa Monica, CA, USA. soday@theangelesclinic.org
authors.forename: S
authors.initials: S
authors.lastname: O'Day
authors.forename: A
authors.initials: A
authors.lastname: Pavlick
authors.forename: C
authors.initials: C
authors.lastname: Loquai
authors.forename: D
authors.initials: D
authors.lastname: Lawson
authors.forename: R
authors.initials: R
authors.lastname: Gutzmer
authors.forename: J
authors.initials: J
authors.lastname: Richards
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: J A
authors.initials: JA
authors.lastname: Thompson
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez
authors.forename: U
authors.initials: U
authors.lastname: Trefzer
authors.forename: P
authors.initials: P
authors.lastname: Mohr
authors.forename: C
authors.initials: C
authors.lastname: Ottensmeier
authors.forename: D
authors.initials: D
authors.lastname: Chao
authors.forename: B
authors.initials: B
authors.lastname: Zhong
authors.forename: C J
authors.initials: CJ
authors.lastname: de Boer
authors.forename: C
authors.initials: C
authors.lastname: Uhlar
authors.forename: D
authors.initials: D
authors.lastname: Marshall
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
authors.forename: Z
authors.initials: Z
authors.lastname: Lang
authors.forename: W
authors.initials: W
authors.lastname: Hait
authors.forename: P
authors.initials: P
authors.lastname: Ho
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy*; D014605:Uveitis / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039564:Integrin alphaV; D003606:Dacarbazine; C486839:intetumumab