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Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study Group

Alessandro Testori, Jon Richards, Eric Whitman, G. Bruce Mann, Jose Lutzky, Luis Camacho, Giorgio Parmiani, Giulio Tosti, John M. Kirkwood, Axel Hoos, Lianng Yuh, Renu Gupta, Pramod K. Srivastava

From the Istituto Europeo di Oncologia; Istituto Nazionale Tumori, Milan, Italy; Lutheran General Cancer Care Center, Park Ridge, IL; Atlantic Health System, Montclair, NJ; Royal Melbourne Hospital, Victoria, Australia; Mount Sinai Comprehensive Cancer Center, Miami Beach, FL; The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of Pittsburgh School of Medicine, Pittsburgh, PA, Bristol-Myers Squibb, Wallingford, CT; Antigenics, New York, NY; and the University of Connecticut School of Medicine, Farmington, CT

Corresponding author: Pramod K. Srivastava, MD, PhD, Center for Immunotherapy of Cancer & Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601; e-mail: srivastava{at}nso2.uchc.edu

Purpose: To assess the antitumor activity of vitespen (autologous, tumor- derived heat shock protein gp96 peptide complexes) by determining whether patients with stage IV melanoma treated with vitespen experienced longer overall survival than patients treated with physician's choice.

Patients and Methods: Patients (N = 322) were randomly assigned 2:1 to receive vitespen or physician's choice (PC) of a treatment containing one or more of the following: dacarbazine, temozolomide, interleukin-2, or complete tumor resection. This open-label trial was conducted at 71 centers worldwide. Patients were monitored for safety and overall survival.

Results: Therapy with vitespen is devoid of significant toxicity. Patients randomly assigned to the vitespen arm received variable number of injections (range, 0 to 87; median, 6) in part because of the autologous nature of vitespen therapy. Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm. Exploratory landmark analyses show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments. Such difference was not detected for substage M1c patients.

Conclusion: These results are consistent with the immunologic mechanism of action of vitespen, indicating delayed onset of clinical activity after exposure to the vaccine. The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the candidate population for a confirmatory study.

P.K.S. is supported by Physicians Health Services Chair in Cancer Immunology, National Institutes of Health Grant No. CA84479, and a sponsored research agreement with Antigenics Inc.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.