The Experts below are selected from a list of 117 Experts worldwide ranked by ideXlab platform
Sandrine Faivre - One of the best experts on this subject based on the ideXlab platform.
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Phase I and pharmacokinetic study of Etaracizumab (Abegrin™), a humanized monoclonal antibody against α_vβ_3 integrin receptor, in patients with advanced solid tumors
Investigational New Drugs, 2008Co-Authors: Catherine Delbaldo, Eric Raymond, Karina Vera, Luz Hammershaimb, Karen Kaucic, Stéphanie Lozahic, Michel Marty, Sandrine FaivreAbstract:This study assessed the safety, immunogenicity, and pharmacokinetics of Etaracizumab, a monoclonal antibody directed against the α_vβ_3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of Etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of Etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of Etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of Etaracizumab warrants further exploration in ongoing phase I/II trials.
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Phase I and pharmacokinetic study of Etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors
Investigational New Drugs, 2007Co-Authors: Catherine Delbaldo, Eric Raymond, Karina Vera, Luz Hammershaimb, Karen Kaucic, Stéphanie Lozahic, Michel Marty, Sandrine FaivreAbstract:This study assessed the safety, immunogenicity, and pharmacokinetics of Etaracizumab, a monoclonal antibody directed against the αvβ3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of Etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of Etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of Etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of Etaracizumab warrants further exploration in ongoing phase I/II trials.
Manuela Buzoianu - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase 2 study of Etaracizumab a monoclonal antibody against integrin αvβ3 dacarbazine in patients with stage iv metastatic melanoma
Cancer, 2010Co-Authors: Peter Hersey, Jeffrey A Sosman, Steven J Oday, Jon M Richards, Agop Y Bedikian, Rene Gonzalez, William H Sharfman, R Weber, Theodore F Logan, Manuela BuzoianuAbstract:BACKGROUND: The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of Etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether Etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive Etaracizumab alone (N = 57) or Etaracizumab + dacarbazine (N = 55). Safety of Etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the Etaracizumab-alone study arm and 12.7% of patients in the Etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the Etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the Etaracizumab-alone study arm and 40.0% of patients in the Etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the Etaracizumab-alone study arm and 2.5 and 2.6 months in the Etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the Etaracizumab-alone study arm and 9.4 months in the Etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.
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A randomized phase 2 study of Etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma
Cancer, 2010Co-Authors: Peter Hersey, Jeffrey A Sosman, Jon M Richards, Agop Y Bedikian, Rene Gonzalez, William H Sharfman, R Weber, Theodore F Logan, Steven J. O'day, Manuela BuzoianuAbstract:BACKGROUND: The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of Etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether Etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive Etaracizumab alone (N = 57) or Etaracizumab + dacarbazine (N = 55). Safety of Etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the Etaracizumab-alone study arm and 12.7% of patients in the Etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the Etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the Etaracizumab-alone study arm and 40.0% of patients in the Etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the Etaracizumab-alone study arm and 2.5 and 2.6 months in the Etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the Etaracizumab-alone study arm and 9.4 months in the Etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.
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a randomized phase 2 study of Etaracizumab a monoclonal antibody against integrin αvβ3 dacarbazine in patients with stage iv metastatic melanoma
Cancer, 2010Co-Authors: Peter Hersey, Jeffrey A Sosman, Steven J Oday, Jon M Richards, Agop Y Bedikian, Rene Gonzalez, William H Sharfman, R Weber, Theodore F Logan, Manuela BuzoianuAbstract:BACKGROUND: The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of Etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether Etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive Etaracizumab alone (N = 57) or Etaracizumab + dacarbazine (N = 55). Safety of Etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the Etaracizumab-alone study arm and 12.7% of patients in the Etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the Etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the Etaracizumab-alone study arm and 40.0% of patients in the Etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the Etaracizumab-alone study arm and 2.5 and 2.6 months in the Etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the Etaracizumab-alone study arm and 9.4 months in the Etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.
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Pharmacodynamic (phase 0) Study Using Etaracizumab in Advanced Melanoma
Journal of Immunotherapy, 2010Co-Authors: Stergios J. Moschos, Manuela Buzoianu, Cindy Sander, Wenjun Wang, Shelley L. Reppert, Laura M. Drogowski, Drazen M. Jukic, Uma N. M. Rao, Charalambos N. Athanassiou, Maja MandicAbstract:AlphaVbeta3 (alphavbeta3) is an important molecule for tumor-induced angiogenesis and is upregulated in metastatic melanoma (MM). We proposed to study the mechanism of action of Etaracizumab, a monoclonal antibody targeting alphavbeta3, in MM. Patients with MM and biopsiable tumor were treated with Etaracizumab in 3 dose cohorts starting from 8 mg/kg. Tumor saturation by Etaracizumab using LM609 immunohistochemical staining of tumor sections was the primary endpoint. Subsequent dose cohorts were defined based on the tumor saturation by Etaracizumab. Secondary end points were analysis of clinical benefit and changes from baseline of several tumor and peripheral blood biomarkers. Eighteen patients were enrolled at 3 dose levels. Etaracizumab showed better melanoma cell saturation at the 8mg/kg and 1 mg/kg dose compared with the 4 mg/kg dose and better vascular endothelial cell saturation at 8 mg/kg compared with lower dose groups. Etaracizumab demonstrated an acceptable safety profile. The optimal biologic dose out of those selected for investigation was 8 mg/kg. Patients treated at the highest dose may have had better clinical benefit secondary to suppression of the activated immediate downstream effector of alphavbeta3 signaling, FAK, in melanoma cells, but this alone did not ultimately affect melanoma cell proliferation or apoptosis. No apparent antiangiogenic or immunomodulatory effects of Etaracizumab were noted.
Catherine Delbaldo - One of the best experts on this subject based on the ideXlab platform.
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Phase I and pharmacokinetic study of Etaracizumab (Abegrin™), a humanized monoclonal antibody against α_vβ_3 integrin receptor, in patients with advanced solid tumors
Investigational New Drugs, 2008Co-Authors: Catherine Delbaldo, Eric Raymond, Karina Vera, Luz Hammershaimb, Karen Kaucic, Stéphanie Lozahic, Michel Marty, Sandrine FaivreAbstract:This study assessed the safety, immunogenicity, and pharmacokinetics of Etaracizumab, a monoclonal antibody directed against the α_vβ_3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of Etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of Etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of Etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of Etaracizumab warrants further exploration in ongoing phase I/II trials.
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Phase I and pharmacokinetic study of Etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors
Investigational New Drugs, 2007Co-Authors: Catherine Delbaldo, Eric Raymond, Karina Vera, Luz Hammershaimb, Karen Kaucic, Stéphanie Lozahic, Michel Marty, Sandrine FaivreAbstract:This study assessed the safety, immunogenicity, and pharmacokinetics of Etaracizumab, a monoclonal antibody directed against the αvβ3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of Etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of Etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of Etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of Etaracizumab warrants further exploration in ongoing phase I/II trials.
Peter Hersey - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase 2 study of Etaracizumab a monoclonal antibody against integrin αvβ3 dacarbazine in patients with stage iv metastatic melanoma
Cancer, 2010Co-Authors: Peter Hersey, Jeffrey A Sosman, Steven J Oday, Jon M Richards, Agop Y Bedikian, Rene Gonzalez, William H Sharfman, R Weber, Theodore F Logan, Manuela BuzoianuAbstract:BACKGROUND: The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of Etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether Etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive Etaracizumab alone (N = 57) or Etaracizumab + dacarbazine (N = 55). Safety of Etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the Etaracizumab-alone study arm and 12.7% of patients in the Etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the Etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the Etaracizumab-alone study arm and 40.0% of patients in the Etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the Etaracizumab-alone study arm and 2.5 and 2.6 months in the Etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the Etaracizumab-alone study arm and 9.4 months in the Etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.
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A randomized phase 2 study of Etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma
Cancer, 2010Co-Authors: Peter Hersey, Jeffrey A Sosman, Jon M Richards, Agop Y Bedikian, Rene Gonzalez, William H Sharfman, R Weber, Theodore F Logan, Steven J. O'day, Manuela BuzoianuAbstract:BACKGROUND: The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of Etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether Etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive Etaracizumab alone (N = 57) or Etaracizumab + dacarbazine (N = 55). Safety of Etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the Etaracizumab-alone study arm and 12.7% of patients in the Etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the Etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the Etaracizumab-alone study arm and 40.0% of patients in the Etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the Etaracizumab-alone study arm and 2.5 and 2.6 months in the Etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the Etaracizumab-alone study arm and 9.4 months in the Etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.
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a randomized phase 2 study of Etaracizumab a monoclonal antibody against integrin αvβ3 dacarbazine in patients with stage iv metastatic melanoma
Cancer, 2010Co-Authors: Peter Hersey, Jeffrey A Sosman, Steven J Oday, Jon M Richards, Agop Y Bedikian, Rene Gonzalez, William H Sharfman, R Weber, Theodore F Logan, Manuela BuzoianuAbstract:BACKGROUND: The alpha v beta 3 (αvβ3) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of Etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the αvβ3 integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether Etaracizumab ± dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive Etaracizumab alone (N = 57) or Etaracizumab + dacarbazine (N = 55). Safety of Etaracizumab ± dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the Etaracizumab-alone study arm and 12.7% of patients in the Etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the Etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the Etaracizumab-alone study arm and 40.0% of patients in the Etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the Etaracizumab-alone study arm and 2.5 and 2.6 months in the Etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the Etaracizumab-alone study arm and 9.4 months in the Etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone. Cancer 2010. © 2010 American Cancer Society.
Eric Raymond - One of the best experts on this subject based on the ideXlab platform.
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Phase I and pharmacokinetic study of Etaracizumab (Abegrin™), a humanized monoclonal antibody against α_vβ_3 integrin receptor, in patients with advanced solid tumors
Investigational New Drugs, 2008Co-Authors: Catherine Delbaldo, Eric Raymond, Karina Vera, Luz Hammershaimb, Karen Kaucic, Stéphanie Lozahic, Michel Marty, Sandrine FaivreAbstract:This study assessed the safety, immunogenicity, and pharmacokinetics of Etaracizumab, a monoclonal antibody directed against the α_vβ_3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of Etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of Etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of Etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of Etaracizumab warrants further exploration in ongoing phase I/II trials.
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Phase I and pharmacokinetic study of Etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors
Investigational New Drugs, 2007Co-Authors: Catherine Delbaldo, Eric Raymond, Karina Vera, Luz Hammershaimb, Karen Kaucic, Stéphanie Lozahic, Michel Marty, Sandrine FaivreAbstract:This study assessed the safety, immunogenicity, and pharmacokinetics of Etaracizumab, a monoclonal antibody directed against the αvβ3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of Etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2–5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of Etaracizumab at doses ranging 1–6 mg/kg. The mean number of weekly infusions was 19 (ranging 5–53). Frequently reported adverse events were grades 1–2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of Etaracizumab ranged 49–180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of >6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of Etaracizumab warrants further exploration in ongoing phase I/II trials.