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

Abstract

Purpose: This open-label study assessed the safety and immunogenicity of two doses and two routes of the anti-idiotypic monoclonal antibody abagovomab (formerlyACA125) 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.

Maintenance therapy in ovarian cancer: Molecular basis and therapeutic approach

“…To evaluate the effect of different doses (0.2 vs. 2 mg), schedules (6 vs. 9 vaccinations) and routes of administration (subcutaneous vs. intramuscular), abagovomab underwent two additional phase i/ii studies that treated 78 patients overall (58,59).…”

Targeted molecular therapies for ovarian cancer: An update and future perspectives (Review)

“…Abagovomab is another murine antiidiotypic antibody against CA125. An open-label phase I trial assessed the safety and immunogenicity of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer (25). The phase I study confirmed the safety, tolerability and immunogenicity of abagovomab.…”

Anti-idiotype antibodies in cancer treatment

“…Interestingly, a correlation between specific humoral response to abagovomab and patients' survival has also emerged, so that randomized, controlled studies are now warranted to possibly prove clinical benefit (Reinartz et al, 2004). However, it seems fair to underline that other subsequent clinical trials on recurrent ovarian cancer (Pfisterer et al, 2006) and on a miscellanea of gynecologic/peritoneal primary tumors (Sabbatini et al, 2006) seem to confirm the encouraging results above. Moreover, pre-clinical data suggest that the integration of IL-6 within the abagovomab formulation -as a fusion protein -might improve efficacy by eliciting even more robust, CA125-specific humoral responses (Reinartz et al, 2003).…”