Phase i ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma

A. Patnaik, G. J. Weiss, K. P. Papadopoulos, C. C. Hofmeister, R. Tibes, A. Tolcher, R. Isaacs, J. Jac, M. Han, F. C. Payumo, M. M. Cotreau, Ramesk K Ramanathan

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)272-280
Number of pages9
JournalBritish Journal of Cancer
Volume111
Issue number2
DOIs
StatePublished - Jul 15 2014
Externally publishedYes

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Multiple Myeloma
Hepatocyte Growth Factor
Pharmacokinetics
Neoplasms
Fatigue
Immunoglobulin G
Hyperkalemia
Hypokalemia
ficlatuzumab
Erlotinib Hydrochloride
Serum
Nausea
Half-Life
Diarrhea
Edema
Therapeutics
Monoclonal Antibodies
Safety
Antibodies

Keywords

  • ficlatuzumab
  • hepatocyte growth factor
  • solid tumours

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase i ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma. / Patnaik, A.; Weiss, G. J.; Papadopoulos, K. P.; Hofmeister, C. C.; Tibes, R.; Tolcher, A.; Isaacs, R.; Jac, J.; Han, M.; Payumo, F. C.; Cotreau, M. M.; Ramanathan, Ramesk K.

In: British Journal of Cancer, Vol. 111, No. 2, 15.07.2014, p. 272-280.

Research output: Contribution to journalArticle

Patnaik, A, Weiss, GJ, Papadopoulos, KP, Hofmeister, CC, Tibes, R, Tolcher, A, Isaacs, R, Jac, J, Han, M, Payumo, FC, Cotreau, MM & Ramanathan, RK 2014, 'Phase i ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma', British Journal of Cancer, vol. 111, no. 2, pp. 272-280. https://doi.org/10.1038/bjc.2014.290
Patnaik, A. ; Weiss, G. J. ; Papadopoulos, K. P. ; Hofmeister, C. C. ; Tibes, R. ; Tolcher, A. ; Isaacs, R. ; Jac, J. ; Han, M. ; Payumo, F. C. ; Cotreau, M. M. ; Ramanathan, Ramesk K. / Phase i ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma. In: British Journal of Cancer. 2014 ; Vol. 111, No. 2. pp. 272-280.
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abstract = "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.",
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AU - Patnaik, A.

AU - Weiss, G. J.

AU - Papadopoulos, K. P.

AU - Hofmeister, C. C.

AU - Tibes, R.

AU - Tolcher, A.

AU - Isaacs, R.

AU - Jac, J.

AU - Han, M.

AU - Payumo, F. C.

AU - Cotreau, M. M.

AU - Ramanathan, Ramesk K

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N2 - 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.

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