Phase 1b Trial of Ficlatuzumab, a Humanized Hepatocyte Growth Factor Inhibitory Monoclonal Antibody, in Combination With Gefitinib in Asian Patients With NSCLC

Hepatocyte growth factor (HGF)/c‐Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV‐299; SCH 900105), a humanized IgG1κ HGF inhibitory monoclonal antibody, prevents HGF/c‐Met pathway ligand–mediated activation. Thi...

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Published in:	Clinical pharmacology in drug development Vol. 7; no. 5; pp. 532 - 542
Main Authors:	Tan, Eng‐Huat, Lim, Wan‐Teck, Ahn, Myung‐Ju, Ng, Quan‐Sing, Ahn, Jin Seok, Shao‐Weng Tan, Daniel, Sun, Jong‐Mu, Han, May, Payumo, Francis C., McKee, Krista, Yin, Wei, Credi, Marc, Agarwal, Shefali, Jac, Jaroslaw, Park, Keunchil
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-06-2018 John Wiley and Sons Inc
Subjects:	Drug dosages ficlatuzumab gefitinib Growth factors lung adenocarcinoma Lung cancer Monoclonal antibodies non‐small cell lung cancer NSCLC Original Manuscript Pharmacology Targeted cancer therapy non-small cell lung cancer ficlatuzumab gefitinib NSCLC lung adenocarcinoma
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Summary:	Hepatocyte growth factor (HGF)/c‐Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV‐299; SCH 900105), a humanized IgG1κ HGF inhibitory monoclonal antibody, prevents HGF/c‐Met pathway ligand–mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non–small cell lung cancer (NSCLC). Patients received intravenous ficlatuzumab either 10 mg/kg (cohort 1; n = 3) or 20 mg/kg (cohort 2; n = 12) every 2 weeks plus oral gefitinib 250 mg daily. Patients tolerated the drug combination well. Four treatment‐related grade 3/4 adverse events were reported in 3 patients (cohort 2). Pharmacokinetic profiles for ficlatuzumab and gefitinib were consistent with prior single‐agent trials. Partial responses were achieved in 5 patients (4 confirmed), all in cohort 2; objective response rate (ORR) was 33% (duration, 1.9–6.4 months). Responding patients had no prior EGFR TKI treatment, 2 without an EGFR mutation. Four additional patients had disease stabilization (cohort 2; duration, 2.7–9.1 months; 42% ORR). The recommended phase 2 dose for ficlatuzumab plus gefitinib 250 mg/day was 20 mg/kg every 2 weeks. This drug combination has shown preliminary dose‐related antitumor activity in advanced NSCLC.
Bibliography:	NCT01039948 Trial registration ID ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Trial registration ID: NCT01039948
ISSN:	2160-763X 2160-7648
DOI:	10.1002/cpdd.427