| General information |
| Database: | DB00695 |
| Objective: | Thisphase I study assessed the safety and pharmacokinetics of bavituximab in patients with advanced solid tumors. |
| Authors: | Gerber DE, et al |
| Title: | Phase I safety and pharmacokinetic study of bavituximab, a chimeric phosphatidylserinetargeting monoclonal antibody, in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21989064 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bavituximab
|
| Target: | membrane phospholipid phosphatidylserine (PS)
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I Safety and Pharmacokinetic Study |
| Key Patients Feature: | This study enrolled adults 18 years or older with evaluable, histologically, or cytologically confirmed refractoryadvanced solid malignancies. Key inclusion criteria included Eastern Cooperative Oncology Group performance statusof 0-1; adequate hematologic, hepatic, and renal functions;prothombin time (PT)/Internationalized Normalized Ratio(INR) and activated partial thromboplastin time (aPTT)within institutional normal limits; and serum Ddimer 2times or less than the upper limit of institutional normal.Major exclusion criteria included any history of thromboembolic events; clinically significant bleeding (defined as ross hematuria, hemoptysis, or gastrointestinal bleeding);history of bleeding diathesis; evidence or history of a hypercoagulable state (e.g., shortened aPTT); ongoing therapywith anticoagulants, nonsteroidal antiinflammatory drugs, or antiplatelet drugs; any history of coronary artery diseaseor cerebrovascular accident; major surgery, chemotherapy, radiation, or investigational therapy within 4 weeks of studytherapy initiation; and prior exposure to chimeric antibodies. Patients with clinically stable, previously treated brainmetastases were eligible for the study. |
| Biomarker: | platelet function and coagulation parameters |
| Biomark Analysis: | Activated partial thromboplastin time was modestly prolonged in vitro at the highest dose tested. |
| Control Group Info: | single arm escalating dose |
| Treatment Info: | Patients in the 0.1 and 0.3 mg/kg cohorts received bavituximab on days 0, 28, 35, and 42. Patients in the 1 and 3 mg/kg cohorts were administered bavituximab on days 0, 7, 14, and 21. |
| Primary End Point: | Safety, pharmacokinetics, and tumor response |
| Secondary End Point: | NA |
| Patients Number: | 26 |
| Trial Results |
| DLT_MTD: | No maximum tolerated dose was reached. Six seriousadverse events occurred in five patients, including one pulmonary embolism at 3 mg/kg, which was theonly doselimiting toxicity (DLT) in the study. |
| Objective Response Rate: | a total of 18patients were evaluable for efficacy, of whom 10 had disease progression and none had an objectiveresponse. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent of these were fatigue (27%), nausea (15%), aPTT prolongation (12%), and pyrexia, rash, and dyspnea (each 8%). Most treatmentrelated adverse events were either grade 1 or 2. Adverse events seemed to occur with similar frequency across dose cohorts. |
| Conclusions: | Bavituximab was well tolerated at doses ranging up to 3 mgkg weekly. Pharmacokinetic studies support a weekly dosing regimen. Additionalphase I and II clinical trials are in progress to investigate bavituximab in combination with chemotherapy and other molecularly targeted agents. |