Last update 01 Nov 2024

VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

Last update 01 Nov 2024

Basic Info

Related Targets

VEGFR1PDGFRc-Kit[+3]

Drugs associated with VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

Motesanib Diphosphate

Target

PDGFR x RET x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

Mechanism

PDGFR antagonists [+5]

Active Org.-

Originator Org.

Amgen, Inc.

Active Indication-

Inactive Indication

Advanced cancer [+14]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

NCT01349088 / WithdrawnPhase 1/2IIT

Phase I/II Trial of Motesanib in Combination With Ixabepilone and Capecitabine in Women With Locally Recurrent or Metastatic Breast Cancer

In 2008 there were more than 40,000 deaths caused by metastatic breast cancer in the United States. The development of new treatment strategies is essential to improve outcome for patients with metastatic breast cancer
There is significant preclinical and clinical evidence indicating that creating new blood vessels (neoangiogenesis) to provide nutrients to solid tumors, including breast cancer, provides the necessary conditions to allow tumor growth. Vascular endothelial growth factor (VEGF) is one of the important molecules regulating new blood vessel formations and subsequent invasion and metastases. As a result, agents that inhibit VEGF are of substantial interest for the treatment of advanced diseases.
This study will further the body of research of motesanib which has been shown in preclinical pharmacology and clinical pharmacology studies to be a potent, orally bioavailable multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, platelet-derived growth factor (PDGF), and Kit receptors.

Start Date01 Dec 2013

Sponsor / Collaborator

Sidney Kimmel Cancer Center at Thomas Jefferson University

[+2]

100 Clinical Results associated with VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

100 Translational Medicine associated with VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

0 Patents (Medical) associated with VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

Literatures (Medical) associated with VEGFR1 x PDGFR x c-Kit x VEGFR2 x RET x VEGFR3

01 Sep 2018·The OncologistQ2 · MEDICINE

E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors

Q2 · MEDICINE

Article

Author: Benson, Al ; Engstrom, Paul ; Giang, Guang-Yu ; Hinshaw, J. Louis ; Stella, Philip ; Meropol, Neal ; Payne, Jennifer ; Mulcahy, Mary ; O'Dwyer, Peter ; Deming, Dustin ; Feng, Yang ; Klein, Leonard ; Teitelbaum, Ursina ; Lubner, Sam

AbstractLessons LearnedRate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer. Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial. Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints.BackgroundNeuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively).MethodsThis was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%–2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS).ResultsForty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1–2. Median PFS was 8.7 months, and overall survival was 27.5 months.ConclusionMotesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3–4 toxicities were encountered. The progression-free survival of 8.7 months in all NETs merits further study.

10 Jun 2007·Journal of Clinical OncologyQ1 · MEDICINE

Multitarget Tyrosine Kinase Inhibition: [And the Winner Is…]

Q1 · MEDICINE

Review

Author: Verweij, Jaap ; de Jonge, Maja

A review.The research of Rosen et al. (2007) entitled "Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors" is reviewed with commentary and referencesRosen et al. report on a phase I study of AMG 706, which inhibits vascular endothelial growth factor receptor 1 (VEGFr1), VEGFr2, VEGFr3, KIT, platelet-derived growth factor receptor, and RET, and thus shares its major targets with sunitinib.AMG 706 seems to be an interesting new multitarget tyrosine kinase inhibitor (MTKI).The different MTKIs yield different activities in different diseases, and as such it seems impossible to favor one over the other without taking disease details into account.

Cancer Management and ResearchQ3 · MEDICINE

Critical appraisal of the use of regorafenib in the management of colorectal cancer

Q3 · MEDICINE

ArticleOA

Author: Anna Manzo ; Teresa Troiani ; Valentina Gambardella ; Lucia Festino ; Alessio Fabozzi ; Floriana Morgillo ; Fortunato Ciardiello ; Ferdinando De Vita ; Michele Orditura ; Erika Martinelli

The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I-II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients.

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