Abstract
BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid tumours.
METHODS: Patients in sequential dose groups received either weekly doses of 1.25, 5.0, or 10 mg kg(-1) or doses of 20 or 30 mg kg(-1) every third week.
RESULTS: Twenty-three patients were enrolled and received TB-403. The most common adverse events (AEs) were fatigue, constipation, pyrexia, dyspnoea, and nausea. One serious AE, a lung embolus in a patient with non-small cell lung cancer treated with 10 mg kg(-1) weekly, was deemed possibly related to TB-403. No dose-limiting toxicities were observed, and a maximum-tolerated dose was not reached. The PK parameters were dose linear and the terminal half-life values ranged from 9 to 14 days. Six patients exhibited stable disease for at least 8 weeks. Two patients, (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated with 5 mg kg(-1) weekly, remained stable for 12 months.
CONCLUSION: TB-403 treatment in this patient population is well tolerated, with a safety profile distinct from that of vascular endothelial growth factor-axis inhibitors.
| Original language | English |
|---|---|
| Journal | B J C |
| Volume | 106 |
| Issue number | 4 |
| Pages (from-to) | 678-84 |
| Number of pages | 7 |
| ISSN | 0007-0920 |
| DOIs | |
| Publication status | Published - 14 Feb 2012 |
Keywords
- Adult
- Aged
- Angiogenesis Inhibitors
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Drug Administration Schedule
- Female
- Humans
- Infusions, Intravenous
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasms
- Pregnancy Proteins
- Clinical Trial, Phase I
- Journal Article
- Multicenter Study
