A Randomized Phase II/III Study of Naptumomab Estafenatox plus IFN alpha versus IFN alpha in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis

作者：Hawkins Robert E^*; Gore Martin; Shparyk Yaroslav; Bondar Vladimir; Gladkov Oleg; Ganev Tosho; Harza Mihai; Polenkov Serhii; Bondarenko Igor; Karlov Petr; Karyakin Oleg; Khasanov Rustem; Hedlund Gunnar; For**erg Goran; Nordle Orjan; Eisen Timothy

来源：Clinical Cancer Research, 2016, 22(13): 3172-3181.

DOI：10.1158/1078-0432.CCR-15-0580

Purpose: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFN alpha versus IFN in metastatic renal cell carcinoma (RCC).
Experimental Design: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 mu g/kg i.v. in three cycles of four once-daily injections) - IFN (9MUs. c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS).
Results: This phase II/III study didnotmeet its primary endpoint. Median OS/PFS forNap + IFN patients was 17.1/5.8months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/ P = 0.41; HR, 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 IL6 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 IL6 benefitted greatly from the 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; HR, 0.59/P = 0.02; HR, 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 patient subgroup. The results warrant further studies with Nap in this subgroup.

• 出版日期2016-7-1