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Title: Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial.
Austin Authors: Davis, Ian D;Brady, Ben;Kefford, Richard F;Millward, Michael;Cebon, Jonathan S ;Skrumsager, Birte K;Mouritzen, Ulrik;Hansen, Lasse Tengbjerg;Skak, Kresten;Lundsgaard, Dorthe;Frederiksen, Klaus Stensgaard;Kristjansen, Paul E G;McArthur, Grant A
Affiliation: Ludwig Oncology Unit, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 10-Mar-2009
Publication information: Clinical Cancer Research 2009; 15(6): 2123-9
Abstract: 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.Open-label, single-arm, two-stage trial.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.antitumor efficacy (response rate).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).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.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.
Gov't Doc #: 19276257
DOI: 10.1158/1078-0432.CCR-08-2663
Journal: Clinical Cancer Research
Type: Journal Article
Subjects: Adult
Interleukin-2 Receptor alpha Subunit.blood
Interleukins.adverse effects.therapeutic use
Melanoma.drug therapy.immunology.mortality.pathology
Middle Aged
Neoplasm Staging
Recombinant Proteins.therapeutic use
T-Lymphocyte Subsets.immunology
Appears in Collections:Journal articles

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