Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial.
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.
Davis
Ian D
ID
Ludwig Oncology Unit, Austin Health, Melbourne, Victoria, Australia.
Brady
Ben
B
Kefford
Richard F
RF
Millward
Michael
M
Cebon
Jonathan
J
Skrumsager
Birte K
BK
Mouritzen
Ulrik
U
Hansen
Lasse Tengbjerg
LT
Skak
Kresten
K
Lundsgaard
Dorthe
D
Frederiksen
Klaus Stensgaard
KS
Kristjansen
Paul E G
PE
McArthur
Grant
G
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
D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D011994:Recombinant Proteins; D000098546:Interleukin-21