Characterization of ipilimumab exposure-efficacy/safety response relationships in subjects with previously treated or untreated advanced melanoma.

8541 Background: Ipilimumab (IPI) is a fully human monoclonal antibody directed against CTLA-4 that is being developed as a novel immunotherapeutic agent against melanoma and other solid tumors. The objective of this analysis was to retrospectively characterize the exposure-response (E-R) relationships for efficacy (overall survival, OS) in subjects with previously untreated advanced melanoma (pu-MEL), and safety (immune related adverse-events, irAEs) in subjects with previously treated advanced melanoma (pt-MEL) or pu-MEL. Methods: The E-R analysis of OS included 498 pu-MEL from a phase III study (CA184024) of IPI administered at 10 mg/kg + dacarbazine (DTIC) or DTIC + placebo; and the E-R analyses of irAE included 1036 subjects from a phase I study (CA184078), 4 phase IIstudies (CA184004/007/008/022) and CA184024 of IPI administered at doses of 0.3, 3 or 10 mg/kg. The relationship between steady‑state IPI trough concentration (Cminss) and OS was described using a Cox proportional hazards model, and the ...