M Aglietta1, C Barone2, M B Sawyer3, M J Moore4, W H Miller5, C Bagalà2, F Colombi6, C Cagnazzo6, L Gioeni6, E Wang7, B Huang7, K D Fly7, F Leone6. 1. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin. Electronic address: massimo.aglietta@ircc.it. 2. Department of Medical Oncology, Catholic University of the Sacred Heart, Rome, Italy. 3. Department of Oncology, University of Alberta, Edmonton. 4. Division of Medical Oncology, Princess Margaret Hospital and University of Toronto, Toronto. 5. Department of Oncology, McGill University, Montreal, Canada. 6. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin. 7. Pfizer Oncology Global Research and Development, Groton, USA.
Abstract
BACKGROUND: Tremelimumab (CP-675,206) is a fully human monoclonal antibody binding to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negative regulatory signal. Combination with standard chemotherapy may strengthen antitumor therapy. This is a phase Ib, multisite, open-label, nonrandomized dose escalation trial evaluating the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab combined with gemcitabine in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Gemcitabine (1000 mg/m(2) on days 1, 8, and 15 of each 28-day cycles) was administrated with escalating doses of i.v. tremelimumab (6, 10, or 15 mg/kg) on day 1 of each 84-day cycle for a maximum of 4 cycles. The first 18 patients had an initial 4-week gemcitabine-only lead-in period. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the first 6 weeks after the first dose of tremelimumab. RESULTS: From June 2008 to August 2011, 34 patients were enrolled and received at least one dose of tremelimumab. No DLTs related to tremelimumab were observed at any dose, even when the maximum dose established for tremelimumab (15 mg/kg) was used. Most frequent grade 3/4 toxicities were asthenia (11.8%) and nausea (8.8%). Only one patient had a serious drug-related event (diarrhea with dehydration). The median overall survival was 7.4 months (95% confidence interval 5.8-9.4 months). At the end of treatment, two patients achieved partial response. Both patients received tremelimumab 15-mg/kg group (n = 2/19, 10.5%). CONCLUSION: Tremelimumab plus gemcitabine demonstrated a safety and tolerability profile, warranting further study in patients with metastatic pancreatic cancer. CLINICALTRIALSGOV ID: NCT00556023.
BACKGROUND: Tremelimumab (CP-675,206) is a fully human monoclonal antibody binding to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negative regulatory signal. Combination with standard chemotherapy may strengthen antitumor therapy. This is a phase Ib, multisite, open-label, nonrandomized dose escalation trial evaluating the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab combined with gemcitabine in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Gemcitabine (1000 mg/m(2) on days 1, 8, and 15 of each 28-day cycles) was administrated with escalating doses of i.v. tremelimumab (6, 10, or 15 mg/kg) on day 1 of each 84-day cycle for a maximum of 4 cycles. The first 18 patients had an initial 4-week gemcitabine-only lead-in period. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the first 6 weeks after the first dose of tremelimumab. RESULTS: From June 2008 to August 2011, 34 patients were enrolled and received at least one dose of tremelimumab. No DLTs related to tremelimumab were observed at any dose, even when the maximum dose established for tremelimumab (15 mg/kg) was used. Most frequent grade 3/4 toxicities were asthenia (11.8%) and nausea (8.8%). Only one patient had a serious drug-related event (diarrhea with dehydration). The median overall survival was 7.4 months (95% confidence interval 5.8-9.4 months). At the end of treatment, two patients achieved partial response. Both patients received tremelimumab 15-mg/kg group (n = 2/19, 10.5%). CONCLUSION: Tremelimumab plus gemcitabine demonstrated a safety and tolerability profile, warranting further study in patients with metastatic pancreatic cancer. CLINICALTRIALSGOV ID: NCT00556023.
Authors: L Marthey; C Mateus; C Mussini; M Nachury; S Nancey; F Grange; C Zallot; L Peyrin-Biroulet; J F Rahier; M Bourdier de Beauregard; L Mortier; C Coutzac; E Soularue; E Lanoy; N Kapel; D Planchard; N Chaput; C Robert; F Carbonnel Journal: J Crohns Colitis Date: 2016-01-18 Impact factor: 9.071
Authors: Kinsey A McCormick; Andrew L Coveler; Gabriela R Rossi; Nicholas N Vahanian; Charles Link; E Gabriela Chiorean Journal: Hum Vaccin Immunother Date: 2016-03-03 Impact factor: 3.452