A Phase I Trial of SD-9427 (Progenipoietin) with a Multipeptide Vaccine for Resected Metastatic Melanoma

• Published in: Clinical cancer research 2003-04, Vol.9 (4), p.1301-1312
• Main Authors: PULLARKAT, Vinod, LEE, Peter P, WOLFE, Richard A, WEBER, Jeffrey S, SCOTLAND, Ronaldo, RUBIO, Valerie, GROSHEN, Susan, GEE, Conway, LAU, Roy, SNIVELY, Jolie, SIAN, Shirley, WOULFE, Susan L
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - metabolism; Chemotherapy; Colony-Stimulating Factors - pharmacology; Colony-Stimulating Factors - therapeutic use; Cytokines - metabolism; Dendritic Cells - metabolism; Epitopes; Female; Flow Cytometry; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Leukapheresis; Male; MART-1 Antigen; Medical sciences; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - surgery; Membrane Glycoproteins - biosynthesis; Middle Aged; Monophenol Monooxygenase - biosynthesis; Neoplasm Proteins - biosynthesis; Peptides - chemistry; Pharmacology. Drug treatments; Recombinant Proteins; Time Factors; Treatment Outcome; Vaccines - metabolism; Vaccines, Subunit - metabolism
• ISSN: 1078-0432; 1557-3265

Purpose: The melanoma tumor antigen epitope peptides MART-1 26–35 (27L) , gp100 209–217 (210M) ,and tyrosinase 368–376 (370D) were emulsified with incomplete Freund’s adjuvant and administered with SD-9427 (progenipoietin), an agonist of granulocyte colony-stimulating factor and the FLT-3 receptor, to evaluate the toxicities of and immune responses to this regimen as primary end points and time to relapse and survival as secondary end points. Experimental Design: Fifteen patients with high-risk resected stage III and IV melanoma were enrolled. Each patient received peptides + incomplete Freund’s adjuvant with SD-9427 at doses of either 10, 20, or 40 μg/kg s.c. for 3 days before and 7 days after each vaccination. Immunizations were administered every month for 6 months and then administered once 6 months later. A leukapheresis to obtain peripheral blood mononuclear cells for immune analyses as well as skin testing with peptides and recall antigens was performed before and after vaccination. IFN- γ release assay, ELISPOT, and MHC-peptide tetramer analysis were performed using peripheral blood mononuclear cells collected before and after vaccination to evaluate peptide-specific cytotoxic T-cell responses. Results: Local pain and granuloma formation and fatigue of grade I or II were the most common side effects. One patient developed antibody-mediated leukopenia and transient grade III neutropenia that resolved after stopping SD-9427. Six of 12 patients tested developed a positive skin test response to one or more of the peptides. Seven of 10 patients tested demonstrated an immune response to at least one peptide when evaluated by IFN-γ release assay and ELISPOT assay after vaccination, as did 11 of 12 patients analyzed by MHC-peptide tetramer assay. Four of 15 patients have relapsed with a median follow-up of 20 months, and 1 patient in this high-risk group has died of disease. Conclusions: SD-9427 with a multipeptide vaccine was generally well tolerated, although one patient developed reversible antibody-mediated neutropenia. These data suggest that the majority of patients with resected melanoma mount an antigen-specific immune response against a multipeptide vaccine administered with SD-9427.