Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 in advanced melanoma: Cancer and Leukemia Group B 509901.
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.
Roberts
John D
JD
Virginia Commonwealth University, Richmond, Virgina 23298-0037, USA. john.d.roberts@vcu.edu
Niedzwiecki
Donna
D
Carson
William E
WE
Chapman
Paul B
PB
Gajewski
Thomas F
TF
Ernstoff
Marc S
MS
Hodi
F Stephen
FS
Shea
Christopher
C
Leong
Stanley P
SP
Johnson
Jeffrey
J
Zhang
Dongsheng
D
Houghton
Alan
A
Haluska
Frank G
FG
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
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