Human Genome Sciences Reports Initial Results of Phase 1 Clinical Trials of HGS-ETR2 (TRAIL-R2 MAB) in Patients With Advanced Cancers
Wednesday September 29, 8:31 am ET
- Results of Ongoing Phase 1 Clinical Studies Demonstrate Safety and Tolerability of HGS-ETR2 and Provide Preliminary Evidence of Biological Activity -
- Data Presented at 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics -
ROCKVILLE, Md., Sept. 29 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - News) today announced that the initial results of an ongoing Phase 1 clinical trial demonstrate the safety and tolerability of HGS-ETR2 (agonistic human monoclonal antibody to TRAIL Receptor 2) in cancer patients with advanced solid tumors, and support continued dose escalation and evaluation of HGS-ETR2 in these patients. Safety, pharmacokinetic and biological activity data from the Phase 1 study were presented today at the 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland. The conference is organized jointly by the European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI) and American Association for Cancer Research (AACR).
A poster entitled "A Phase 1 Safety and Pharmacokinetic (PK) Study of an Agonistic, Fully Human Monoclonal Antibody, HGS-ETR2, to the TNF-Related Apoptosis-Inducing Ligand Receptor 2 (TRAIL-R2) in Patients with Advanced Cancer" (Abstract #197) presented data on eighteen patients treated to date in an ongoing open-label, dose-escalation clinical trial.(1) All of the eighteen patients had received prior cancer therapy; seventeen had received prior chemotherapy. The patients were enrolled into four cohorts (0.01, 0.03, 1.0, or 3.0 mg/kg) and received HGS-ETR2 administered intravenously with repeat dosing on a 21-day schedule. An additional cohort is planned at 10.0 mg/kg. The primary purpose of the ongoing Phase 1 trial is to determine the safety and tolerability of HGS-ETR2 in patients with advanced solid malignancies. Pharmacokinetics and disease response also are being evaluated.
Results to date of the ongoing Phase 1 clinical trial demonstrate that HGS-ETR2 can be administered safely and repetitively to patients with advanced solid malignancies at doses up to and including 3.0 mg/kg intravenously every 21 days. HGS-ETR2 was well tolerated with minimal toxicities. No clear evidence of drug-related hematologic or hepatic toxicity has been observed at the doses administered to date. The MTD has not been reached, and accrual in the trial continues at higher doses. Preliminary pharmacokinetic data were consistent with expectations based on preclinical studies of HGS-ETR2. In the four patients treated at the 3.0 mg/kg dose level, the terminal elimination half-life of HGS-ETR2 was prolonged, averaging 11 days. Plasma concentrations were observed to be in a range associated with preclinical evidence of biological activity. Stable disease was observed in six patients for two cycles or more.
Hilary Calvert, M.D., Professor of Medical Oncology, Newcastle University and a consultant at Newcastle General Hospital, Newcastle upon Tyne, UK, said, "A primary goal of cancer therapy is the selective induction of apoptosis in cancer cells. TRAIL induces apoptosis in a wide variety of cancer cells by activating its death receptors, TRAIL-R1 and TRAIL-R2. HGS-ETR2 is a high- affinity fully human monoclonal antibody agonistic and specific to TRAIL-R2. It induces apoptosis in tumor cell lines expressing TRAIL-R2 and induces tumor regression in nonclinical models. The initial clinical results presented today demonstrate that HGS-ETR2 is well tolerated and there does not appear to be any drug-related normal tissue toxicity. We have observed stable disease in a number of these heavily pretreated and refractory patients. Further dose-escalation and evaluation of HGS-ETR2 is appropriate, and treatment continues at the 10 mg/kg dose level."
David C. Stump, M.D., Executive Vice President, Drug Development, said, "The initial data from our ongoing Phase 1 clinical trial of HGS-ETR2 are encouraging. The data show that HGS-ETR2 is well tolerated and can be safely and repetitively administered to patients with advanced solid tumors. We have not yet reached the maximum tolerated dose. I am particularly encouraged that stable disease has been observed in a number of the patients treated to date. The Phase 1 study of HGS-ETR2 fits into a broad program of clinical trials of our three agonistic TRAIL receptor antibodies. We look forward to continuing to elucidate the potential role of HGS-ETR2 as a treatment for solid tumor malignancies."
Human Genome Sciences, using genomic techniques, originally identified the TRAIL Receptor-2 protein as a member of the tumor necrosis factor receptor super-family. The company's own studies, as well as those conducted by others, show that TRAIL Receptor 2 plays a key role in triggering apoptosis, or programmed cell death, in tumors.(2-6) Human Genome Sciences took the approach of developing human monoclonal antibodies that would bind the receptor and stimulate the TRAIL Receptor-2 protein to trigger apoptosis in cancer cells, in much the same way that the native TRAIL ligand (tumor necrosis factor-related apoptosis-inducing ligand) triggers it, but with the advantage of a longer half-life and an exclusive specificity for TRAIL Receptor 2. The TRAIL Receptor-2 agonistic human monoclonal antibody, HGS- ETR2, was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.(7) Human Genome Sciences holds the commercial rights to the drug.
For more information about HGS-ETR2, see hgsi.com. Health professionals interested in more information about trials involving HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, hgsi.com, or by calling (240) 314-4400, extension 3550.
Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based protein and antibody drugs to patients.
HGS and Human Genome Sciences are trademarks of Human Genome Sciences, Inc.
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
Footnotes:
1. J. S. de Bono, H. Calvert, et al. A Phase 1 Safety and
Pharmacokinetic (PK) Study of an Agonistic, Fully Human Monoclonal
Antibody, HGS-ETR2, to the TNF-Related Apoptosis-Inducing Ligand
Receptor 2 (TRAIL-R2), in Patients with Advanced Cancer. 16th EORTC-
NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004:
(Abstract #197).
2. L.H. Le, et al. Phase 1 Study of a Fully Human Monoclonal Antibody to
the Tumor Necrosis Factor-Related Apoptosis-Inducting Ligand Death
Receptor 4 (TRAIL-R1) in Subjects with Advanced Solid Malignancies or
Non-Hodgkin's Lymphoma. American Society of Clinical Oncology Annual
Meeting, 2004: Abstract #2533.
3. G.V. Georgakis, et al. Selective Agonistic Monoclonal Antibodies to
the TRAIL Receptors R1 and R2 Induce Cell Death and Potentiate the
Effect of Chemotherapy and Bortezomib in Primary and Cultured Lymphoma
Cells. American Society of Clinical Oncology Annual Meeting, 2004:
Abstract #6595.
4. TRAIL R2-mAb, a human agonistic monoclonal antibody to tumor necrosis
factor-related apoptosis inducing ligand receptor 2, affects tumor
growth and induces apoptosis in human tumor xenograft models in vivo.
Robin C. Humphreys, Ralph F. Alderson, Eliel Bayever, Kevin Connolly,
Gil H. Choi, Norma Lynn Fox, Gilles Gallant, Krzystof J.
Grzegorzewski, Viktor Roschke, Theodora W. Salcedo, Jing Zhang, Junli
Zhang, Vivian R. Albert. 94th AACR Annual Meeting. Abstract 642.
5. TRAIL-R2 mAb, a human agonistic monoclonal antibody to tumor necrosis
factor-related apoptosis inducing ligand receptor 2, induces apoptosis
in human tumor cells. Ralph F. Alderson, Charles E. Birse, Kevin
Connolly, Gil H. Choi, Norma Lynn Fox, Gilles Gallant, Ina Han, Robin
C. Humphreys, Ron Johnson, Palanisamy Kanakaraj, Vikram Patel, Oxana
Pickeral, Laurie Pukac, Viktor Roschke, Theodora Salcedo, Tara Shah,
Junli Zhang, Vivian R. Albert. 94th AACR Annual Meeting. Abstract
963.
6. Ashkenazi A. et al. Safety and anti-tumor activity of recombinant
soluble APO2 ligand. J Clin Inv July 1999; 104(2): 155-162.
7. (HGSI Press Release) Human Genome Sciences And Cambridge Antibody
Technology Commit To Exclusive Development Of Antibody To Trail
Receptor 2. May 20, 2002. |
