Presentation Abstract

Program#/Poster#: 185.2/DD19
Title: ANG1005: A promising new Engineered Peptide Compound (EPiC) for patients with advanced solid tumors and brain metastases
Location: South Hall A
Presentation Time: Sunday, Oct 18, 2009, 9:00 AM -10:00 AM
Authors: R. KURZROCK1, N. GABRAIL2, S. MOULDER1, A. BRENNER3, Z. GUO1, D. BOUCHARD4, W. CHURCHILL4, P. BENTO4, D. FITSIALOS5, B. FRAITAG6, A. NEALE7, *J.-P. CASTAIGNE4, J. SARANTOPOULOS3;
1MD Anderson, Houston, TX; 2Gabrail Cancer Ctr., Canton, OH; 3Cancer Therapy and Res. Center, UT Hlth. Sci. Ctr. San Antonio, San Antonio, TX; 4Angiochem Inc., Montreal, QC, Canada; 5Intrinsik Hlth. Sci. Inc., Mississauga, ON, Canada; 6MD, Paris, France; 7WinPharm Associates, Danville, CA
Abstract: Introduction: Approximately 170,000 patients with solid tumors develop brain metastases in the US annually and this incidence is expected to rise. Challenges to treatment stem from the inability of most drugs to cross the BBB in sufficient quantities without the limitation of systemic toxicity. Angiochem is developing a broad pipeline of new drugs uniquely capable of crossing the BBB to treat brain diseases. ANG1005, a novel taxane derivative, is the first from the Engineered Peptide Compounds (EPiC) platform to be developed clinically. Studies show that ANG1005 enters the brain by targeting low-density lipoprotein receptor-related protein (LRP), one of the most highly expressed receptors on the BBB and that ANG1005 also enters tumor cells via LRP, which is upregulated in various cancer cells including metastatic cancer cells.
Methods: As of 18-May-2009, 47 patients with advanced solid tumors/brain metastases have received ANG1005 by IV infusion at doses of 30-700 mg/m2 q21d without premedication. Study objectives include characterizing the safety/tolerability of ANG1005, identifying the MTD, and obtaining preliminary PK and antitumor information. Severity of AEs is assessed using CTCAE, v.3.
Results: Exploration of 650 mg/m2 as MTD is currently ongoing. Although neutropenia, leucopenia, thrombocytopenia and anemia have developed, these cases have been milder than expected based on clinical observation with paclitaxel and have been manageable with standard treatments. Preliminary neurocognitive data show no evidence of CNS toxicity; in fact, data from one patient with a minor tumor response showed significant improvement in memory, processing speed and executive function after 6, 12 and 24 weeks of therapy. Biological data show that ANG1005 does not elicit an immune response, even in patients who have received 6 treatment cycles. Pharmacokinetic data show a linear relationship between dose and bioavailability. Radiology data indicate potential efficacy in tumor regression/slowing tumor progression, with 9 out of 11 patients evaluated at doses above 300 mg/m2 experiencing stable disease or better at 6 weeks.
Conclusion: Data to date support the continued development of ANG1005 as a safe, tolerable and potentially efficacious treatment option for patients suffering from brain metastases.
Disclosures:   R. Kurzrock, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); N. Gabrail, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); S. Moulder, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); A. Brenner, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Z. Guo, None; D. Bouchard, Angiochem Inc., A. Employment (full or part-time); W. Churchill, Angiochem Inc., A. Employment (full or part-time); P. Bento, Angiochem Inc., A. Employment (full or part-time); D. Fitsialos, Angiochem Inc., F. Consultant/Advisory Board; B. Fraitag, None; A. Neale, Angiochem Inc., F. Consultant/Advisory Board; J. Castaigne, Angiochem Inc., A. Employment (full or part-time); J. Sarantopoulos, Angiochem Inc., B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received).
Keyword(s): ANG1005
Brain Metastases
Solid Tumors
[Authors]. [Abstract Title]. Program No. XXX.XX. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online.

2009 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.




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