Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 in advanced melanoma: Cancer and Leukemia Group B 509901.

Abstract

High-dose interleukin-2 (IL-2) is the only approved immunologic therapy for advanced melanoma, but response rates are low and significant toxicities limit treatment to otherwise healthy patients. g209-2M is a nanopeptide engineered to mimic an epitope of the gp100 melanocyte differentiation protein that is recognized in a human leukocyte antigen (HLA)-restricted manner by melanoma tumor-infiltrating lymphocytes in some patients. Previous reports indicated that administration of the g209-2M peptide could induce g209-reactive circulating T cells in patients with melanoma and that the combination of g209-2M and high-dose IL-2 might be a more active treatment than high-dose IL-2 alone. Low-dose IL-2 is not active but has significant biologic effects, and because of a different toxicity profile, it can be offered to most patients. The primary objective of this cooperative group phase 2 study was to determine the activity of the combination of g209-2M and low-dose IL-2 in advanced melanoma. Twenty-six HLA appropriate patients with advanced melanoma received subcutaneous g209-2M peptide once every 3 weeks and subcutaneous IL-2 (5 million IU/m) daily for 5 days during the first and second weeks. Patients were monitored for tumor response, toxicity, and induction of g209-reactive circulating T cells. There were no objective responses. There were no toxic deaths and no grade 4 toxicities. More than half of the patients experienced some grade 2 toxicity and one quarter experienced grade 3 toxicity. There was no convincing evidence by enzyme-linked immunospot or tetramer analysis of induction of g209-reactive circulating T cells. The combination of g209-2M and low-dose IL-2 is safe and tolerable but inactive against advanced melanoma. Absence of evidence of immunization raises concerns for peptide-based immunization strategies with concurrent IL-2.

• Authors: John D Roberts, Donna Niedzwiecki, William E Carson, Paul B Chapman, Thomas F Gajewski, Marc S Ernstoff, F Stephen Hodi, Christopher Shea, Stanley P Leong, Jeffrey Johnson, Dongsheng Zhang, Alan Houghton, Frank G Haluska, Cancer and Leukemia Group B
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2006 Jan-Feb Vol. 29 Issue 1 Pg. 95-101 ISSN: 1524-9557 [Print] United States
• PMID: 16365605 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Interleukin-2
• Membrane Glycoproteins
• PMEL protein, human
• Peptide Fragments
• Peptides
• g209-2M melanoma peptide
• gp100 Melanoma Antigen

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cancer Vaccines (administration & dosage)
• Dose-Response Relationship, Drug
• Female
• Humans
• Interleukin-2 (administration & dosage)
• Leukocytes, Mononuclear (drug effects, immunology)
• Male
• Melanoma (immunology, therapy)
• Membrane Glycoproteins (immunology, therapeutic use)
• Middle Aged
• Neoplasm Recurrence, Local (therapy)
• Peptide Fragments (immunology, therapeutic use)
• Peptides
• Skin Neoplasms (immunology, therapy)
• gp100 Melanoma Antigen