A Randomized Phase 2/3 Study of Naptumomab Estafenatox + IFN-{alpha} vs IFN-{alpha} in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis

Purpose: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + interferon α (IFN) versus IFN in metastatic renal cell carcinoma (RCC). Experimental Design: In a randomized, open-label, multicenter, phase 2/3 study, 513 RCC patients received Nap (15 µg/kg intravenously in three cycles of four once daily injections) + IFN (9 MU subcutaneously three times weekly) or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). Results: This phase 2/3 study did not meet its primary endpoint. Median OS/PFS for Nap+IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (p=0.56, hazard ratio 1.08/p=0.41, hazard ratio 0.92). Post-hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL-6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n=130) having concentrations below median of anti-SEA/E-120 and IL-6 benefitted greatly from addition of Nap. In SG median OS/PFS for the patients treated with Nap+IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (p=0.02, hazard ratio 0.59/p=0.02, hazard ratio 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile. Conclusions: The study did not meet its primary endpoint. Nap+IFN has an acceptable safety profile and results from post-hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker defined RCC patients subgroup. The results warrant further studies with Nap in this subgroup.

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