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Background Trebananib is an anti-angiogenic peptibody under investigation in patients with advanced cancer. This study evaluated the pharmacokinetic (PK) drug-drug interaction of paclitaxel and trebananib. Patients and methods Patients with advanced solid tumors received weekly 80 mg/m intravenous (IV) paclitaxel (3 weeks on/1 week off) with weekly 15 mg/kg IV trebananib starting at Week 2. Blood samples for PK analysis were collected at Week 1 (paclitaxel alone), Week 6 (paclitaxel and trebananib), and Week 8 (trebananib alone). An absence of interaction was to be concluded if the 90 % confidence intervals (CI) for the differences in paclitaxel exposure fell within the 0.80-1.25 interval. Results The primary study was conducted between 7/2012 and 10/2013. Thirty-five patients were enrolled and 34 received both treatments. Most patients were white (91 %) and female (59 %); mean age was 61 years. The most common tumor types were ovarian (32 %) and bladder (27 %), 71 % of patients had stage IV disease, and all had Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. PK parameter analysis was done on patients with evaluable PK data at both assessments (with and without concomitant therapy; n = 28). The geometric least squares mean (GLSM) ratio (90 % CI) of paclitaxel AUC with and without trebananib was 1.17 (1.10, 1.25). The GLSM ratio (90 % CI) of trebananib AUC with and without paclitaxel was 0.92 (0.87, 0.97). The most common adverse events were fatigue, local edema, peripheral edema, and nausea. Conclusions This study showed no evidence of clinically meaningful PK interaction between paclitaxel and trebananib. [ABSTRACT FROM AUTHOR]

Introduction: Angiosarcomas are rare malignant endothelial cell tumors which have up-regulation of the angiopoietin system [e.g., Tie2 and Angiopoietin 2 (Ang2)]. Trebananib is a novel agent targeting Angiopoietin 1 and Angiopoietin 2. Methods: Trebananib 30 mg/kg was administered weekly until progressive disease or unacceptable toxicity. The primary endpoint was response rate by RECIST v1.1. Correlatives included: (1) baseline tumor expression of Ang2/Tie2 by immunohistochemistry, (2) serum levels of Ang1 and Ang2, (3) pre- and post-treatment phospho-receptor tyrosine kinase and (4) MYC/FLT-4 amplification status. Results: Sixteen patients were enrolled [median age 68 years (24-91), 38 % male, median number of prior therapies 2.5 (1-7)]. No responses were observed in 12 evaluable patients. Estimated median and 12-week progression-free survival rate were 7 weeks (95 % 6-8) and 25 % (95 % CI 11-58 %), respectively. Median overall survival was 28 weeks (95 % CI 17-48). There were two (12.5 %) patients who experienced grade 3 adverse event and one (6.3 %) patient who experienced grade 4 adverse event that was considered at least possibly related to treatment. Conclusions: Trebananib was well tolerated. Lack of response in the first stage of a Simon 2 stage design led to closure of this study. Prolonged PFS was observed in four pts, lasting 3.4-5.5 months. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of trebananib (AMG 386)-a first-in-class angiopoietin-1/2 antagonist peptide-Fc fusion protein-in Japanese patients, we conducted a phase 1, dose escalation study. Methods: Eligible patients were men or women, aged between 20 and 74 years, who had histologically or cytologically confirmed advanced solid tumors refractory to standard treatment. Trebananib (3, 10, and 30 mg/kg) was administered intravenously over 60 min in weekly cycles. Results: From June 2009 to April 2010, a total of 18 patients (6 for each dose cohort) were enrolled into the study. Trebananib was tolerated at all dose levels. No dose-limiting toxicities were observed. The most common adverse events were peripheral edema, constipation, fatigue, and pyrexia. Exposure to trebananib appeared to increase according to the dose administered. Serum clearance appeared to be similar across the dose range with the mean terminal-phase half-life ranging from 93.9 to 95.9 h. No neutralizing antibodies were detected. Tumor response was assessed in 18 patients. Of these, one patient with colon cancer in the 3-mg/kg cohort and one with bladder cancer in the 30-mg/kg cohort had partial responses as their best responses. These 2 patients were on treatment at the time of data cutoff (January 17, 2012). Conclusion: Trebananib was tolerated and showed acceptable safety profile in Japanese patients with advanced solid tumors. The pharmacokinetic profiles were similar to those in the previous studies in the United States. Trebananib also showed evidence of durable antitumor activity in some patients. [ABSTRACT FROM AUTHOR]