title: 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.affiliation: Virginia Commonwealth University, Richmond, Virgina 23298-0037, USA. john.d.roberts@vcu.edu
authors.forename: John D
authors.initials: JD
authors.lastname: Roberts
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Christopher
authors.initials: C
authors.lastname: Shea
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Leong
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Johnson
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.forename: Alan
authors.initials: A
authors.lastname: Houghton
authors.forename: Frank G
authors.initials: FG
authors.lastname: Haluska
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D010455:Peptides; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D058951:gp100 Melanoma Antigen
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; C548638:g209-2M melanoma peptide; D058951:gp100 Melanoma Antigen