Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma
Mené sur 41 patients atteints d'une tumeur solide ou d'un myélome multiple réfractaire de stade avancé, cet essai de phase I évalue la dose maximale tolérée, la toxicité et l'activité antitumorale du ficlatuzumab, un inhibiteur du facteur de croissance des hépatocytes IgG1k, seul ou en combinaison avec l'erlotinib
Background: Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1
κ 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 less than or equal to20 mg kg–1. Common adverse events (AEs) included peripheral oedema, fatigue and nausea. Three patients experienced grade greater than or equal to3 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.