Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1-2 studyReport as inadecuate

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Journal for ImmunoTherapy of Cancer

, 2:2

Clinical-Translational Cancer Immunotherapy


BackgroundDespite the positive impact of targeted therapies on metastatic renal cell carcinoma mRCC, durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 IL-21, a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor.

MethodsIn this phase 1-2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 10–50 mcg-kg on days 1–5 and 15–19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated.

ResultsIn phase 1 n = 19, the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg-kg-day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib.

ConclusionIL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC.

Trial Identifier: NCT00389285

KeywordsInterleukin-21 Sorafenib Renal cell carcinoma RCC Immunotherapy Cytokine VEGF Tyrosine kinase inhibitors TKI Durable response Targeted therapy Electronic supplementary materialThe online version of this article doi:10.1186-2051-1426-2-2 contains supplementary material, which is available to authorized users.

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Author: Shailender Bhatia - Brendan Curti - Marc S Ernstoff - Michael Gordon - Elisabeth I Heath - Wilson H MillerJr - Igor Puza


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