Michael B Atkins1, Gwenaelle Gravis2, Kazimierz Drosik2, Tomasz Demkow2, Piotr Tomczak2, Shirley S Wong2, M Dror Michaelson2, Toni K Choueiri2, Benjamin Wu2, Lynn Navale2, Douglas Warner2, Alain Ravaud2. 1. Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA. mba41@georgetown.edu. 2. Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
Abstract
PURPOSE: Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma. PATIENTS AND METHODS: Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival. RESULTS: Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B. CONCLUSION: Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.
PURPOSE: Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma. PATIENTS AND METHODS: Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival. RESULTS: Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B. CONCLUSION: Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.
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