Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.
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.
Sabbatini
Paul
P
Memorial Sloan-Kettering Cancer Center, New York, New York, Franklin Square Hospital, Baltimore, MD, USA, and University of Marburg, Germany.
Dupont
Jakob
J
Aghajanian
Carol
C
Derosa
Felicia
F
Poynor
Elizabeth
E
Anderson
Sybil
S
Hensley
Martee
M
Livingston
Phillip
P
Iasonos
Alexia
A
Spriggs
David
D
McGuire
William
W
Reinartz
Silke
S
Schneider
Sally
S
Grande
Cathy
C
Lele
Shashikant
S
Rodabaugh
Kerry
K
Kepner
James
J
Ferrone
Soldano
S
Odunsi
Kunle
K
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
D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma