Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

Open-label, single-arm, two-stage trial.

ELIGIBILITY CRITERIA:

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.

PRIMARY OBJECTIVE:

antitumor efficacy (response rate).

SECONDARY OBJECTIVES:

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: Ian D Davis, Ben Brady, Richard F Kefford, Michael Millward, Jonathan Cebon, Birte K Skrumsager, Ulrik Mouritzen, Lasse Tengbjerg Hansen, Kresten Skak, Dorthe Lundsgaard, Klaus Stensgaard Frederiksen, Paul E G Kristjansen, Grant McArthur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 6 Pg. 2123-9 (Mar 15 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19276257 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-2 Receptor alpha Subunit
• Interleukins
• Recombinant Proteins
• interleukin-21

Topics

• Adult
• Aged
• Female
• Humans
• Interleukin-2 Receptor alpha Subunit (blood)
• Interleukins (adverse effects, therapeutic use)
• Male
• Melanoma (drug therapy, immunology, mortality, pathology)
• Middle Aged
• Neoplasm Staging
• Recombinant Proteins (therapeutic use)
• T-Lymphocyte Subsets (immunology)