A phase I dose escalation trial of CP-675206 (tremelimumab) in combination with gemcitabine in patients with chemotherapy-naive metastatic pancreatic cancer.

Abstract

4134 Background: CP-675,206 (tremelimumab) is a fully human monoclonal antibody which binds to the CTLA4 molecule on the surface of activated T lymphocytes and T regulatory cells. It is thought to stimulate the immune system to attack tumor cells by blocking the negative regulatory signal of CTLA4. Primary objective of the study is to determine the maximum tolerated dose (MTD) and evaluate the safety profile of CP-675,206 in combination with gemcitabine for the treatment of patients with previously untreated metastatic pancreatic cancer. Methods: All patients received a 1-month gemcitabine-only lead-in period. Gemcitabine (1,000 mg/m2) was administered for 3 weekly doses followed by one week of rest. For patients who successfully completed the lead-in period, escalating doses of CP-675,206 were added to gemcitabine. Three dose levels of CP-675,206 were tested (6 mg/kg, 10 mg/kg, and 15 mg/kg). CP-675,206 was administered intravenously on day 1 of each 12-week cycle. Dose limiting toxicities (DLTs) related to CP-675,206 therapy were evaluated during the first 6 weeks after the first dose of CP-675,206. Results: A total of 18 pts (M/F = 12/6; median age approximately 53; range 29-73) were enrolled in the study. The median number of CP-675,206 cycles was 2 (range 1-3). No DLTs related to CP-675,206 were observed at any dose level. Most frequent grade 3-4 toxicities were anemia (4/18), transaminases increase (3/18), bilirubin increase (3/18). All G3-4 AEs were considered related to gemcitabine or disease progression. Two out of 17 evaluable pts obtained confirmed partial responses. Conclusions: CP-675,206 in combination with gemcitabine was well tolerated up to the dose level of 15 mg/kg. A next step of the study is ongoing. It will evaluate the safety profile of CP-675,206 when administered simultaneously to gemcitabine without a gemcitabine-only lead-in period. No significant financial relationships to disclose.