Phase I Study of Abagovomab in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• Published in: Clinical cancer research Vol. 12; no. 18; pp. 5503 - 5510
• Main Authors: SABBATINI, Paul, DUPONT, Jakob, MCGUIRE, William, REINARTZ, Silke, SCHNEIDER, Sally, GRANDE, Cathy, LELE, Shashikant, RODABAUGH, Kerry, KEPNER, James, FERRONE, Soldano, ODUNSI, Kunle, AGHAJANIAN, Carol, DEROSA, Felicia, POYNOR, Elizabeth, ANDERSON, Sybil, HENSLEY, Martee, LIVINGSTON, Phillip, IASONOS, Alexia, SPRIGGS, David
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-09-2006
• Subjects: abagovomab; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibody Formation - drug effects; Antineoplastic agents; Biological and medical sciences; CA-125 Antigen - blood; CA-125 Antigen - immunology; Cohort Studies; Drug Administration Routes; Fallopian Tube Neoplasms - blood; Fallopian Tube Neoplasms - drug therapy; Fallopian Tube Neoplasms - immunology; Female; Histocompatibility Antigens Class II - blood; Histocompatibility Antigens Class II - metabolism; Humans; Interferon-gamma - biosynthesis; Medical sciences; Middle Aged; monoclonal antibody; ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - immunology; Peritoneal Neoplasms - blood; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - immunology; Pharmacology. Drug treatments; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Human; Ovary; Treatment; Female genital system; Primary; Phase I trial; Malignant tumor; Fallopian tube; Peritoneum; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-2670

Purpose: 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.
Experimental Design: 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.