title: Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.
abstract: OBJECTIVE
  This open-label study assessed the safety and immunogenicity of two doses and two routes of the anti-idiotypic monoclonal antibody abagovomab (formerly ACA125) in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.
  
  
  METHODS
  Eligible patients from the three participating institutions were any stage at diagnosis, had relapsed, and had complete or partial response to additional chemotherapy. Patients were randomized to receive abagovomab at 2.0 versus 0.2 mg and i.m. versus s.c. for four immunizations every 2 weeks and then monthly for two additional immunizations. Planned evaluation included interval physical examinations and laboratory assessments with immune assessment, including HLA typing, human anti-mouse antibody, ELISA, and enzyme-linked immunospot. Patients were required to remain on study until week 10 (the first post-baseline Ab3 determination) to be considered for immunologic assessment. The primary end points were safety and immunogenicity primarily determined by Ab3 response.
  
  
  RESULTS
  Forty-two patients received at least one vaccination and were eligible for safety analysis. Thirty-three patients were available for Ab3 analysis (removed for progression of disease, 6; withdrawal of consent, 2; unrelated adverse event, 1). The most common adverse events were self-limited pain at injection site, myalgia, and fever. No hematologic or nonhematologic toxicity grade>2 related to immunization was seen. Ab3 was detectable in all patients (median, 236,794 ng/mL); none of route of administration (P=0.6268), dose (P=0.4602), or cohort (P=0.4944) was statistically significant in terms of effect on maximum post-baseline Ab3 titer. Human anti-mouse antibody was not detectable at baseline but was present in all patients at week 16 (range, 488-45,000 ng/mL).
  
  
  CONCLUSIONS
  Immunization with abagovomab is well tolerated and induced robust Ab3 responses at the two doses and routes tested. A phase III randomized study with abagovomab (2.0 mg s.c.) is warranted.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, Franklin Square Hospital, Baltimore, MD, USA, and University of Marburg, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Jakob
authors.initials: J
authors.lastname: Dupont
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.forename: Felicia
authors.initials: F
authors.lastname: Derosa
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Poynor
authors.forename: Sybil
authors.initials: S
authors.lastname: Anderson
authors.forename: Martee
authors.initials: M
authors.lastname: Hensley
authors.forename: Phillip
authors.initials: P
authors.lastname: Livingston
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: David
authors.initials: D
authors.lastname: Spriggs
authors.forename: William
authors.initials: W
authors.lastname: McGuire
authors.forename: Silke
authors.initials: S
authors.lastname: Reinartz
authors.forename: Sally
authors.initials: S
authors.lastname: Schneider
authors.forename: Cathy
authors.initials: C
authors.lastname: Grande
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Kerry
authors.initials: K
authors.lastname: Rodabaugh
authors.forename: James
authors.initials: J
authors.lastname: Kepner
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects; D018394:CA-125 Antigen / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D004333:Drug Administration Routes; D005185:Fallopian Tube Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000097:blood / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma