| General information |
| Database: | DB00479 |
| Objective: | Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2. |
| Authors: | Hong DS, et al |
| Title: | a phase I, openlabel study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma. |
| Journal: | Clin Genitourin Cancer. |
| Year: | 2014 |
| PMID: | 24365125 |
| Trial Design |
| Clinical Trial Id: | NCT00861419 |
| Agent: | trebananib
|
| Target: | Angiopoietin2, Angiopoietin1
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | trebananib combined with sorafenib or sunitinib |
| Study Type: | open-label, phase Ib study |
| Key Patients Feature: | Patients (more than and equal to 18years) had an Eastern Cooperative Oncology Group (ECOG) performance status of less than and equal to 2; andadequate hematological, renal, and hepatic function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. |
| Primary End Point: | adverse event incidence and pharmacokinetics. |
| Secondary End Point: | NA |
| Patients Number: | 37 |
| Trial Results |
| DLT_MTD: | A dose-limiting toxicity (DLT) was any grade 3 or greater toxicity, except for the following modifications: transient grade 3 infusion reactions lasting more than 2 hours; grade 3 fatigue or grade 4 neutropenia for more than 7 days; grade 3 or 4 nausea, diarrhea, vomiting, or neutropenia with fever above 38.5¡ãC; grade 4 aspart ate or alanine aminotransferase greater than 10 times the upper limit of normal; and grade 4 thrombocytopenia, anemia, or hypertension. |
| Objective Response Rate: | Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib) |
| Disease Control Rate: | NA |
| Median Time to Progression: | The median TTP (95% CI) was 40.3 weeks (22.9 weeks - 127.4 weeks) for patients across both trebananib plus sorafenib dose cohorts. Across the trebananib plussunitinib dose cohorts (n = 19), the median TTP (95% CI) was 48.0 weeks (30.6 weeks - 98.3 weeks). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | During trebananib plus sorafenib administration (n = 17), the most common treatmentrelated adverse events (TRAEs) included rash (71%), diarrhea (71%), hypertension (65%), and fatigue (65%); grade more than and equal to 3 TRAEs (41%); and 14% of patients had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (74%), fatigue (68%), hypertension (58%), and decreased appetite (58%); grade more than and equal to 3 TRAEs (68%); and 42% of patients had peripheral edema. |
| Conclusions: | The toxicities of trebananib 3 mgkg or 10 mgkg I.V. plus sorafenib or sunitinib in RCC they were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed. |