AACR 2000
Abstract #3463

Autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96) in patients with metastatic melanoma

O Eton, M East, MI Ross, CA Savary, SP Tomasovic, D Reitsma, E Hawkins, PK Srivastava. Univ of Texas, MD Anderson Cancer Center, Houston, TX 77030; Antigenics, LLC, New York, NY 10111; Univ of Connecticut, Farmington, CT 06030.

Gp96, a nonpolymorphic heat shock protein, associates with intracellular peptides. Autologous tumor (AT)-derived HSPPC-96 can elicit potent tumor-specific T-cell responses and protective immunity in animal models. This Phase I trial sought to evaluate the safety of HSPPC-96 given ID at 2.5, 25 or 100 µg/dose weekly x 4 and to select a dose based on induction of antitumor immunity and clinical activity. Since January 1998, 36 patients were enrolled after routine resection of a >3-cm melanoma metastasis in stage IV (26 patients) or advanced stage III (10 patients) setting. Sixteen patients had indicator lesions. Thirty patients had prior systemic therapy. HSPPC-96 was prepared from specimens as small as 2 grams. There were no serious toxicities. Lack of DTH response to DNCB in 11 patients (31%) correlated with presence of indicator lesions (P = .01), but not with clinical stage. There was no DTH reactivity through week eight to either HSPPC-96 or 105 irradiated AT cells. One patient at each dose level had stabilization or mixed response after initial progression in nodal or lung metastases, all lasting more than seven months. Eleven of 12 stage IV adjuvant patients (eight stage IVM1 B) remain free of disease a median of 11+ months. With nine-month median follow-up, 19 patients remain on study, with 29 (80%) alive. Ongoing in vitro studies to confirm induction of antitumor immunity will be required to determine the dose range for future clinical trials with HSPPC-96.