Final toxicity results of a phase I dose-escalation trial of tremelimumab (CP-675206) in combination with gemcitabine in chemotherapy-naive patients (pts) with metastatic pancreatic cancer.

4081 Background: Tremelimumab (CP-675206) is a fully human monoclonal antibody that binds to cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on T lymphocytes and T regulatory cells. It is thought to stimulate the immune system to attack tumor cells by blocking the CTLA4-negative regulatory signal. The primary objective of this phase I study was to determine the maximum tolerated dose and evaluate the safety of tremelimumab plus gemcitabine in pts with previously untreated metastatic pancreatic cancer. Methods: In Part A of the study, pts received gemcitabine only during a 1-mo lead-in period. Gemcitabine (1,000 mg/m2) was administered on days 1, 8, and 15 of a 4-wk cycle. Escalating doses of tremelimumab (6 mg/kg, 10 mg/kg, and 15 mg/kg) were then administered intravenously on day 1 of each 12-wk cycle. In Part B, tremelimumab at 2 dose levels (10 mg/kg and 15 mg/kg) was administered simultaneously with gemcitabine. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the firs...