TY - JOUR
T1 - Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage TV Malignant melanoma without prior treatment
T2 - A phase Lla trial
AU - Davis, Ian D.
AU - Brady, Ben
AU - Kefford, Richard F.
AU - Millward, Michael
AU - Cebon, Jonathan
AU - Skrumsager, Birte K.
AU - Mouritzen, Ulrik
AU - Hansen, Lasse Tengbjerg
AU - Skak, Kresten
AU - Lundsgaard, Dorthe
AU - Frederiksen, Klaus Stensgaard
AU - Kristjansen, Paul E.G.
AU - McArthur, Grant
PY - 2009/3/15
Y1 - 2009/3/15
N2 - 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 (rlL-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-rlL-21 antibodies. rIL-21 (30 μg/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 l 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+ Tcells, and mRNA for IFN-γ, perforin, and granzyme B in CD8+ Tand NK cells. Conclusions: rIL-21 administered at 30 μg/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.
AB - 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 (rlL-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-rlL-21 antibodies. rIL-21 (30 μg/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 l 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+ Tcells, and mRNA for IFN-γ, perforin, and granzyme B in CD8+ Tand NK cells. Conclusions: rIL-21 administered at 30 μg/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.
UR - http://www.scopus.com/inward/record.url?scp=63449095686&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-2663
DO - 10.1158/1078-0432.CCR-08-2663
M3 - Article
C2 - 19276257
AN - SCOPUS:63449095686
VL - 15
SP - 2123
EP - 2129
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 6
ER -