spot difference
  • Sign In
  • Register
  • Cart (0)
Home > References > 2007 > Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.

Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.

Rosen, L., Kurzrock, R., Mulay, M., Van Vugt, A., Purdom, M., Ng, C., Silverman, J., Koutsoukos, A., Sun, Y.N., Bass, M.B., Xu, R.Y., Polverino, A., Wiezorek, J.S., Chang, D.D., Benjamin, R., Herbst, R.S.
Journal   Clin Oncol.
Species  
Analytes Measured   PlGF , Flt-1 VEGFR1
Matrix Tested   Serum
Year   2007
Volume   25
Page Numbers   2369-76
Application   Cytokines and Chemokines
Abstract
PURPOSE: AMG 706 is an investigational, orally bioavailable inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and stem-cell factor receptor. This phase I, dose-finding study evaluated the safety, pharmacokinetics, and pharmacodynamics of AMG 706 in patients with refractory advanced solid tumors. PATIENTS AND

METHODS: AMG 706 was administered at escalating doses of 50 to 175 mg once daily or 25 mg bid for the first 21 days of a 28-day cycle. The 125-mg once-daily dose was also administered continuously. The maximum-tolerated dose (MTD), safety, pharmacokinetics, tumor response, and serum levels of proangiogenic markers were determined.

RESULTS: Seventy-one patients received AMG 706. The MTD was 125 mg once daily administered continuously. The most frequent adverse events were fatigue (55%), diarrhea (51%), nausea (44%), and hypertension (42%). Plasma AMG 706 concentrations increased in a dose-proportional manner with no accumulation after multiple doses. Five patients (7%) had a partial response, 35 patients (49%) had stable disease (at least through day 50), and 31 patients (44%) had progressive disease. Changes in tumor size correlated significantly with an increase in placental growth factor (P = .003) and a decrease in soluble kinase domain receptor (P = .001).

CONCLUSION: In this study of patients with advanced refractory solid tumors, AMG 706 was well tolerated and displayed favorable pharmacokinetics and evidence of antitumor activity. Additional studies of AMG 706 as monotherapy and in combination with various agents are ongoing.

View Publications
View Publications

Related Products

U-PLEX Human VEGFR-1/Flt-1 Antibody Set
VEGFR-1/Flt-1 | Human
U-PLEX Human VEGFR-1/Flt-1 Assay
VEGFR-1/Flt-1 | Human
Singleplex
U-PLEX Human VEGFR-1/Flt-1 384-well Assay
VEGFR-1/Flt-1 | Human
Singleplex
U-PLEX Metastasis Combo 1 (human)
E-Selectin, MMP-1, MMP-2, MMP-7, MMP-9 (total), P-Selectin, VEGFR-1/Flt-1 | Human
Multiplex
R-PLEX Mouse VEGFR-1/Flt-1 Assay
VEGFR-1/Flt-1 | Mouse
Singleplex
R-PLEX Mouse VEGFR-1/Flt-1 Antibody Set
VEGFR-1/Flt-1 | Mouse
U-PLEX Human PlGF 384-Well Assay
PlGF | Human
Singleplex
U-PLEX Human PlGF Antibody Set
PlGF | Human
U-PLEX Angiogenesis Combo 1 (human)
FGF (basic), PlGF, Tie-2, VEGF-A, VEGF-D | Human
Multiplex
U-PLEX Human PlGF Assay
PlGF | Human
Singleplex
V-PLEX Plus Human Biomarker 39-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Human Biomarker 39-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
Human Flt-1 Antibody
VEGFR-1/Flt-1
Human PlGF Antibody
PlGF
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Human PlGF Kit
PlGF | Human
Singleplex
V-PLEX Plus Human Flt-1 Kit
VEGFR-1/Flt-1 | Human
Singleplex
V-PLEX Plus Angiogenesis Panel 1 (human) Kit
FGF (basic), PlGF, Tie-2, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Human Flt-1 Kit
VEGFR-1/Flt-1 | Human
Singleplex
U-PLEX Immuno-Oncology Group 1 (human) 384-well Assays
BAFF-R/TNFRSF13C, BCMA/TNFRSF17, CD20, CD27, CD28, CD40L (soluble), CD276/B7-H3, CTACK, CTLA-4, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF (basic), FLT3L, Fractalkine, G-CSF, GITR/TNFRSF18, GITRL/TNFSF18, GM-CSF, gp130 (soluble), Granzyme A, Granzyme B, GRO-α, HAVCR2/TIM-3, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, LAG3, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-5, OX40/TNFRSF4, PD1 (epitope 1), PD1 (epitope 2), PD-L1 (epitope 1), PD-L2, PlGF, RANKL/TNFSF11, Tie-2, TIGIT, TLR1, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, VEGF-D, YKL-40 | Human
Multiplex
U-PLEX Immuno-Oncology Group 1 (human) Assays
APRIL/TNFSF13, BAFF-R/TNFRSF13C, BCMA/TNFRSF17, CD20, CD27, CD28, CD40L (soluble), CD276/B7-H3, CTACK, CTLA-4, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, E-Selectin, FGF (basic), FLT3L, Fractalkine, Galectin-9, G-CSF, GITR/TNFRSF18, GITRL/TNFSF18, GM-CSF, gp130 (soluble), Granzyme A, Granzyme B, GRO-α, HAVCR2/TIM-3, HVEM/TNFRSF14, I-309, ICOS-L/B7-H2, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, LAG3, LIGHT/TNFSF14, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIG, MIP-1α, MIP-1β, MIP-5, MMP-1, MMP-7, MMP-9 (total), Nectin-4, OX40/TNFRSF4, PD1 (epitope 1), PD1 (epitope 2), PD-L1 (epitope 1), PD-L1 (epitope 2), PD-L2, Pentraxin 3, Perforin, PlGF, proMMP-9, P-Selectin, RAGE (soluble), RANKL/TNFSF11, RANTES, S100A12, Tie-2, TIGIT, TLR1, TNF-α, TNF-β, TNF-RI, TNF-RII, TPO, TRAIL, TSLP, VEGF-A, VEGF-D, VEGFR-1/Flt-1, YKL-40 | Human
Multiplex
Angiogenesis Control Pack 1
FGF (basic), PlGF, Tie-2, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
V-PLEX Human PlGF Kit
PlGF | Human
Singleplex
V-PLEX Angiogenesis Panel 1 Human Kit
FGF (basic), PlGF, Tie-2, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters