A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours
Research output: Contribution to journal › Journal article › Research › peer-review
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 |
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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 |
- 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
Research areas
ID: 167431253