Final efficacy results of NCIC CTG IND.202: A randomized phase II study of recombinant interleukin-21 (rIL21) in patients with recurrent or metastatic melanoma (MM).

9032 Background: rIL21 is a T-cell derived cytokine with antitumor activity dependent on NK cells or CD8+ T cells through induction of central and effector memory cells. A previous phase II study demonstrated an ORR of 22.5% in previously untreated patients with MM. We conducted a multicentre randomized phase II study of MM evaluating the efficacy, toxicity, pharmacokinetics, immunogenicity, and biomarkers of rIL21 versus dacarbazine (DTIC). Methods: Eligible patients: Recurrent or MM, with either maximum tumour lesion size of < 50 mm or LDH < 2.5 x ULN and prior therapy with BRAF/MEK inhibitors allowed. Patients were treated with either rIL-21, 30 µg /kg/day dose IV daily x 5 days weeks 1, 3, 5 q 8 weeks or dacarbazine (DTIC) 1000 mg/m2 IV q 3 weeks. The primary objective was to compare progression free survival (PFS). The trial was designed to detect a hazard ratio of 1.75 with one-sided alpha of 0.1; 58 progression events were required to provide 80% power. Results: 64 patients were randomized, 32 in the rIL-21 arm and 32 in the DTIC arm. The Table summarizes key demographic and efficacy endpoints. Common rIl21 related adverse events were fatigue, rash, diarrhea, nausea, myalgia and elevated liver enzymes. At least one dose reduction/ interruption or discontinuation occurred in 32 (100%) and 27 (96.4%) of rIL21 and DTIC patients. Conclusions: Despite encouraging efficacy in prior phase I/II studies, the results suggest that rIL-21 is comparable to DTIC in this patient population. Additional biomarker analysis from this study is pending and combination studies are currently ongoing. Clinical trial information: NCT00514085. [Table: see text]