Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC]) in patients with advanced melanoma

摘要: LBA9011 Background: Tremelimumab, a fully human anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody was tested in phase III study to compare the overall survival (OS) with standard, single-agent chemotherapy. Methods: Pts unresectable stage IIIc-IV melanoma without brain metastasis, LDH below 2x ULN, and no prior systemic treatment for advanced were randomized 1:1 either tremelimumab 15 mg/kg IV q90d, or physician's choice of TMZ 200 mg/m2 p.o. d1–5 q28d DTIC 1,000 q21d (chemotherapy arm). Primary endpoint OS, secondary endpoints included response, durable tumor 6-mo PFS, safety. 537 deaths would provide 90% power detect 33% improvement true median OS an unstratified log-rank test at 2-sided significance level 0.045. Two equally spaced interim analyses planned based on group sequential design using Lan-DeMets alpha beta spending approach O'Brien-Fleming boundary. Results: 655 pts e...