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The Immune Adjuvant Properties of Front-line Carboplatin-Paclitaxel: A Randomized Phase 2 Study of Alternative Schedules of Intravenous Oregovomab Chemoimmunotherapy in Advanced Ovarian Cancer

Braly, Patricia*; Nicodemus, Christopher F.; Chu, Christina; Collins, Yvonne§; Edwards, Robert; Gordon, Alan; McGuire, William; Schoonmaker, Christopher MS**; Whiteside, Theresa††; Smith, Lesley Mary‡‡; Method, Michael§§

doi: 10.1097/CJI.0b013e31818b3dad
Clinical Studies

Oregovomab is a monoclonal antibody that recognizes CA125 and forms circulating immune complexes that can elicit immunity against both tumor antigen and tumor. This study was designed to assess combining this immunotherapy at 2 dosing schedules with front-line chemotherapy in patients with advanced ovarian cancer. Forty patients with stage III/IV carcinomas were randomized to receive a 2 mg oregovomab infusion either the same day [simultaneous infusion (SIM)] or 1 week after [1-week delayed (OWD)] standard carboplatin-paclitaxel chemotherapy at cycles 1, 3, and 5, then quarterly for up to 11 antibody doses. The primary end point was antibody response to oregovomab. Secondary end points included cellular immune response, response rate to front-line treatment, and progression-free survival. A different immune response pattern was observed between the SIM arm and the OWD arm, baseline plasma cytokines were balanced. Humoral immunity occurred more rapidly (P=0.0033) and with greater magnitude in the SIM arm. Absolute lymphocyte counts decreased in the SIM arm at cycles 3 and 5 compared with baseline. Treatment emergent CA125-specific cellular immunity was measured more commonly with SIM (P=0.04) and clinical parameters directionally favored this schedule. The immune responses were stronger than those measured in a previous maintenance monoimmunotherapy protocol. Immunotherapy-associated toxicity was minimal in this study. Front-line chemotherapy with carboplatin-paclitaxel has immune adjuvant properties when combined with oregovomab immunotherapy; however, schedule is important. SIM strategies of carboplatin and paclitaxel should be further studied with oregovomab and other antigen-specific cancer immunotherapy approaches.

*Hematology and Oncology Specialists, Covington, LA

Advanced Immune Therapeutics Inc, Wellesley Hills

**Veristat Inc, Holliston, MA

Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia

Gynecology Oncology Division, Magee-Womens Hospital of UPMC

††University of Pittsburgh Cancer Institute, Pittsburgh, PA

§Division of Gynecologic Oncology, University of Illinois at Chicago, Chicago, IL

M D Anderson Cancer Center Orlando, Orlando, FL

The Harry and Jeanette Weinberg Cancer Institute, Medical Administration, Oncology, Baltimore, MD

‡‡United Therapeutics Inc, Research Triangle Park, NC

§§Michiana Hematology Oncology, PC, South Bend, IN

Financial Disclosure: Christopher F. Nicodemus is a former employee of United Therapeutics who sponsored this project. He also has stock ownership in and is receiving consulting fees from United Therapeutics. All other authors received remuneration from Unither for this study and its precursor study. L. Mary Smith is an employee of United Therapeutics.

Reprints: Patricia Braly, Hematology and Oncology Specialists, 39 Starbrush Circle, Covington, LA 70433 (e-mail: patricia.braly@salco.net).

Received for publication January 11, 2008; accepted June 25, 2008

© 2009 Lippincott Williams & Wilkins, Inc.