Patnaik, A, Weiss, GJ, Papadopoulos, KP, Hofmeister, CC, Tibes, R, Tolcher, A, Isaacs, R, Jac, J, Han, M, Payumo, FC, Cotreau, MM and Ramanathan, RK (2014) Phase i ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma. British Journal of Cancer. pp. 272-280.

Abstract

Background:Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1 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<sup>-1</sup> intravenously every 2 weeks (q2w). Additional patients were treated at the RP2D erlotinib.Results:Forty-one patients enrolled at doses <20 mg kg<sup>-1</sup>. 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 <sup>-1</sup> kg<sup>-1</sup>), 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<sup>-1</sup> 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. 2014 Cancer Research UK

Item Type:	Article
Additional Information:	NIBR author: Han, M institute: NIBR- address only contributor address: A. Patnaik, Clinical Research, South Texas Accelerated Research Therapeutics (START), 4383 Medical Drive, San Antonio, TX 78229, United States. E-mail: amita.patnaik@start.stoh.com
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/23418