title: Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial.
abstract: OBJECTIVE
  Human interleukin-21 (IL-21) is a class I cytokine that mediates activation of CD8(+) T cells, natural killer (NK) cells, and other cell types. We report final clinical and biological results of a phase II study of recombinant human IL-21 (rIL-21) in patients with metastatic melanoma.
  
  
  METHODS
  Open-label, single-arm, two-stage trial.
  
  
  METHODS
  unresectable metastatic melanoma, measurable disease by Response Evaluation Criteria in Solid Tumors, no prior systemic therapy (adjuvant IFN permitted), adequate major organ function, good performance status, no significant autoimmune disease, and life expectancy at least 4 months.
  
  
  OBJECTIVE
  antitumor efficacy (response rate).
  
  
  OBJECTIVE
  safety, blood biomarkers, and generation of anti-rIL-21 antibodies. rIL-21 (30 microg/kg/dose) was administered by intravenous bolus injection in 8-week cycles (5 dosing days followed by 9 days of rest for 6 weeks and then 2 weeks off treatment).
  
  
  RESULTS
  Stage I of the study comprised 14 patients. One confirmed complete response (CR) was observed, and as per protocol, 10 more patients were accrued to stage II (total n = 24: 10 female and 14 male). Best tumor response included one confirmed CR and one confirmed partial response, both with lung metastases. Treatment was overall well tolerated. Biomarker analyses showed increases in serum soluble CD25, frequencies of CD25(+) NK and CD8(+) T cells, and mRNA for IFN-gamma, perforin, and granzyme B in CD8(+) T and NK cells.
  
  
  CONCLUSIONS
  rIL-21 administered at 30 microg/kg/d in 5-day cycles every second week is biologically active and well tolerated in patients with metastatic melanoma. Confirmed responses, including one CR, were observed.
authors.affiliation: Ludwig Oncology Unit, Austin Health, Melbourne, Victoria, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Ben
authors.initials: B
authors.lastname: Brady
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Birte K
authors.initials: BK
authors.lastname: Skrumsager
authors.forename: Ulrik
authors.initials: U
authors.lastname: Mouritzen
authors.forename: Lasse Tengbjerg
authors.initials: LT
authors.lastname: Hansen
authors.forename: Kresten
authors.initials: K
authors.lastname: Skak
authors.forename: Dorthe
authors.initials: D
authors.lastname: Lundsgaard
authors.forename: Klaus Stensgaard
authors.initials: KS
authors.lastname: Frederiksen
authors.forename: Paul E G
authors.initials: PE
authors.lastname: Kristjansen
authors.forename: Grant
authors.initials: G
authors.lastname: McArthur
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007378:Interleukins / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D011994:Recombinant Proteins; D000098546:Interleukin-21