Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma
| Autor: | M M Cotreau, M Han, Ramesh K. Ramanathan, Amita Patnaik, F C Payumo, J. Jac, R Isaacs, Glen J. Weiss, Raoul Tibes, C C Hofmeister, Anthony W. Tolcher, Kyriakos P. Papadopoulos |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Nausea Peripheral edema Cohort Studies Erlotinib Hydrochloride Pharmacokinetics Neoplasms Internal medicine Ficlatuzumab Antineoplastic Combined Chemotherapy Protocols medicine Humans Adverse effect Protein Kinase Inhibitors solid tumours Aged Aged 80 and over ficlatuzumab business.industry Antibodies Monoclonal Middle Aged hepatocyte growth factor Pharmacodynamics Clinical Study Quinazolines Female Erlotinib medicine.symptom Multiple Myeloma business medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2014.290 |
| Popis: | Background: Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1κ inhibitory monoclonal antibody, was evaluated for recommended phase II dose (RP2D), safety, pharmacokinetics (PKs), antidrug antibody (ADA), pharmacodynamics (PDs) and antitumour activity as monotherapy or combined with erlotinib. Methods: Patients with solid tumours received ficlatuzumab 2, 5, 10 or 20 mg kg–1 intravenously every 2 weeks (q2w). Additional patients were treated at the RP2D erlotinib. Results: Forty-one patients enrolled at doses ⩽20 mg kg–1. Common adverse events (AEs) included peripheral oedema, fatigue and nausea. Three patients experienced grade ⩾3 treatment-related hyperkalaemia/hypokalaemia, diarrhoea or fatigue. Best overall response (44%) was stable disease (SD); median duration was 5.5 months (0.4–18.7 months). One patient has been on therapy with SD for >4 years. Pharmacokinetics of ficlatuzumab showed low clearance (0.17–0.26 ml h–1 kg–1), a half-life of 6.8–9.4 days and dose-proportional exposure. Ficlatuzumab/erlotinib had no impact on the PK of either agent. No ADAs were detected. Ficlatuzumab increased serum HGF levels. Conclusions: Recommended phase II dose is 20 mg kg–1 q2w for ficlatuzumab monotherapy or with erlotinib. Preliminary antitumour activity and manageable AEs were observed. Pharmacokinetics were dose-proportional and consistent with other IgG therapeutics. Ficlatuzumab was not immunogenic, and serum HGF was a potential PD marker. |
| Databáze: | OpenAIRE |
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