Anti-HGF Recombinant Antibody (Ficlatuzumab) (CAT#: TAB-749)

Figure 1 Ficlatuzumab exposure as a function of cycle 1 dose.

(A) Ficlatuzumab concentration-time profiles by dose for cycle 1. (B) Comparison of ficlatuzumab AUC0τ in patients administered ficlatuzumab alone vs ficlatuzumab with concurrent erlotinib treatment in cycle 1. Abbreviations: AUC0τ=area under the concentration-time curve from time zero to immediately before the next dose; Erlo=erlotinib.

Patnaik, A., Weiss, G. J., Papadopoulos, K. P., Hofmeister, C. C., Tibes, R., Tolcher, A.,... & Cotreau, M. M. (2014). Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma. British journal of cancer, 111(2), 272.

Figure 2 Serum HGF levels were measured using validated ELISA assay (R&D Systems).

(A) Higher HGF levels were observed in trial cancer patients than in normal controls. Pre-dosing HGF levels for P05538 patients were derived from the average of levels at screening and C1D1 pre-dosing. Hepatocyte growth factor levels from normal controls (41 cases) were measured using the same method. Median, quartile, maximum, minimum were indicated in the box plot. On average, cancer patients in P05538 have 5.8-fold higher HGF than normal control (3.93 vs 0.68 ng ml–1), and the difference is statistically significant based on Student's t-test (P<0.001). (B) Serum HGF levels increases after ficlatuzumab treatment. Hepatocyte growth factor fold change from baseline was derived from for each time point as follows: (HGF–HGF at C1D1-pre)/HGF at C1D1-pre. Average fold change at each time point from all cohorts were plotted as a function of time relative to the start of ficlatuzumab treatment. Abbreviations: C1D1=cycle 1 day 1; HGF=hepatocyte growth factor.

Patnaik, A., Weiss, G. J., Papadopoulos, K. P., Hofmeister, C. C., Tibes, R., Tolcher, A.,... & Cotreau, M. M. (2014). Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma. British journal of cancer, 111(2), 272.

Figure 3 Pharmacodynamic changes in liver tumor biopsies.

Liver biopsies from a single patient predose (left-hand side of A–E) and 3 days after ficlatuzumab 20 mg/kg (right-hand side of A–E) to detect levels of p-Met (A), p-MAPK (B), Ki-67 (C), CD31 (D), and tumor HGF(E).

Tabernero, J., Elez, M. E., Herranz, M., Rico, I., Prudkin, L., Andreu, J.,... & Credi, M. (2014). A pharmacodynamic/pharmacokinetic study of ficlatuzumab in patients with advanced solid tumors and liver metastases. Clinical Cancer Research, 20(10), 2793-2804.

Figure 4 Ficlatuzumab pharmacokinetics.

A, concentration time profiles. Serum concentrations of ficlatuzumab are plotted as a function of treatment visit for each patient. Dashed lines indicate expected dosing times for cycle 1 day 1, cycle 2 day 1, and cycle 3 day 1 (0, 14, and 28 doses since the first ficlatuzumab dose, respectively). Four patients who withdrew before their cycle 2 dose were included up to their last recorded sample point. Ficlatuzumab Cmax (B) and AUC0→∞ (C) as a function of cycle 1 dose. AUC0→∞, area under the concentration-time curve extrapolated to infinite time.

Tabernero, J., Elez, M. E., Herranz, M., Rico, I., Prudkin, L., Andreu, J.,... & Credi, M. (2014). A pharmacodynamic/pharmacokinetic study of ficlatuzumab in patients with advanced solid tumors and liver metastases. Clinical Cancer Research, 20(10), 2793-2804.