Human Genome Sciences Reports Results of Phase 2 Clinical Trial of
HGS-ETR1 In Patients With Non-Small Cell Lung Cancer
- Results support continued study of HGS-ETR1 in combination with
chemotherapy in non-small cell lung cancer -
Human Genome Sciences, Inc. (Nasdaq: HGSI - News) announced today
that the results of a Phase 2 clinical trial demonstrate that HGS-
ETR1 (mapatumumab) is well tolerated and can be administered safely
in patients with advanced non-small cell lung cancer (NSCLC).(1)
Stable disease was observed in a number of patients.
Data on 32 patients were presented yesterday in Barcelona, Spain, at
the 11th World Conference on Lung Cancer in a poster
entitled "Results of a Phase 2 Trial of HGS-ETR1 (Agonistic Human
Monoclonal Antibody to TRAIL Receptor 1) in Subjects with
Relapsed/Recurrent Non-Small Cell Lung Cancer." The trial, which was
conducted in the United States, was a multi-center, open-label study
to evaluate the efficacy, safety and tolerability of HGS-ETR1 in
patients with relapsed or refractory non-small cell lung cancer.(2)
Patients enrolled in the trial received 10 mg/kg doses of HGS-ETR1
administered as an intravenous infusion 21 days apart in the absence
of disease progression. The primary objective of the study was to
evaluate tumor response. The secondary objectives were to evaluate
the safety and tolerability of HGS-ETR1, and to determine plasma
concentrations of HGS-ETR1 for use in a population pharmacokinetic
analysis.
Patients participating in the study had previously received up to 7
different cancer treatment regimens (median of 3). The data
presented demonstrated that HGS-ETR1 was well tolerated, with no
patients discontinuing therapy due to drug-related toxicity, and
that HGS-ETR1 can safely be administered intravenously every 21 days
at doses of 10 mg/kg. No immunogenic responses were observed. Stable
disease was observed in 29% (9/32) of the patients treated, with 8
patients receiving at least 4 cycles of therapy. Plasma
concentrations in the NSCLC study population were within the range
expected based on previous Phase 1/2 experience.
F. Anthony Greco, M.D., a study investigator and Medical Director of
The Sarah Cannon Research Institute, Nashville, said, "The results
of the Phase 2 study of HGS-ETR1 in heavily treated patients with
advanced non-small cell lung cancer support further evaluation of
HGS-ETR1 in this indication in combination with chemotherapeutic
agents. Non-small cell lung cancer represents a significant medical
need. Fewer than half of the patients who are newly diagnosed with
non-small cell lung cancer are candidates for surgery. The majority
of these patients present with incurable locally advanced or
metastatic disease. (3-4) We look forward to continuing to evaluate
the potential of HGS-ETR1 in non-small cell lung cancer in
combination with chemotherapeutic agents."
David C. Stump, M.D., Executive Vice President, Drug Development,
said, "HGS-ETR1 is the subject of a broadening program of clinical
study. We are pleased to have available the results of the Phase 2
trial in patients with advanced non-small cell lung cancer. The data
presented demonstrate that HGS- ETR1 can be safely and repetitively
administered to these patients. We note that stable disease was
observed in a number of these very ill patients who had received
multiple regimens of anti-cancer therapy before entering the study
of HGS-ETR1. We recently reported the positive interim results of a
separate Phase 2 clinical trial of HGS-ETR1 in advanced non-
Hodgkin's lymphoma and look forward to presentation of the complete
results of that study at an appropriate scientific meeting later in
2005.(5) The results of an ongoing Phase 2 study in patients with
advanced colorectal cancer are also expected later this year.(6) In
addition, we continue to enroll patients into two Phase 1b trials of
HGS-ETR1 in combination with chemotherapy."
Human Genome Sciences, using genomic techniques, originally
identified the TRAIL receptor-1 and TRAIL receptor-2 proteins as
members of the tumor necrosis factor receptor super-family. The
company's own studies, as well as those conducted by others, show
that TRAIL receptor 1 and TRAIL receptor 2 play a key role in
triggering apoptosis, or programmed cell death, in tumors. Human
Genome Sciences took the approach of developing human monoclonal
antibodies that would bind to specific TRAIL receptors and stimulate
the TRAIL receptor-1 and TRAIL receptor-2 proteins 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 1 or TRAIL receptor
2, respectively. Human Genome Sciences' own clinical and preclinical
studies, along with published results in the scientific literature,
demonstrate that agonistic antibodies to the death domain-containing
TRAIL receptors have significant potential to provide novel
therapeutic options to patients with a variety of cancer types,
including non-small cell lung cancer.(7-26) The TRAIL receptor-1
agonistic human monoclonal antibody, HGS- ETR1, and one of the
company's two TRAIL receptor-2 human monoclonal antibodies, HGS-
ETR2, were made in a collaboration between Human Genome Sciences and
Cambridge Antibody Technology.(27) The second TRAIL receptor-2 human
monoclonal antibody, HGS-TR2J, was made in a collaboration with the
Pharmaceutical Division of Kirin Brewery Company, Ltd.(28-29)
Non-small cell lung cancer accounts for approximately 75-80 percent
of all lung cancers. It is estimated that more than 173,000 new
cases and more than 160,000 deaths of lung cancer occurred in the
United States in 2004. It is currently the leading cause of cancer
death in this country in both men and women.(3)
For more information about HGS-ETR1, see
www.hgsi.com/products/ETR1.html. 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, www.hgsi.com/products/request.html, or by calling (240)
314-4400, extension 3550.
The mission of Human Genome Sciences is to discover, develop,
manufacture and market innovative drugs that serve patients with
unmet medical needs, with a primary focus on protein and antibody
products.
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. Bonomi P, Greco FA, et al. Results of a Phase 2 trial of
HGS-ETR1
(agonistic human monoclonal antibody to TRAIL receptor 1) in
subjects
with relapsed/recurrent non-small cell lung cancer. 11th
World
Conference on Lung Cancer. July 4, 2005. Abstract #1851.
2. (HGSI Press Release) Human Genome Sciences Completes Patient
Enrollment in a Phase 2 Clinical Trial of HGS-ETR1 for the
Treatment
of Non-Small Cell Lung Cancer. November 30, 2004.
3. Jemal A, Tiwari RC, Murray T, et al. Cancer Statistics,
2004. Cancer
2004; 54(1):8-29.
4. Lara P, Lau DHM, Davies A, et al. Current Status and Future
Directions in Advanced Non-Small Cell Lung Cancer. Oncology
Special
Edition 2002; 4:129-135.
5. (HGSI Press Release) Human Genome Sciences Reports Interim
Results of
Phase 2 Clinical Trial of HGS-ETR1 in Patients with Advanced
Non-
Hodgkin's Lymphoma. June 13, 2005.
6. (HGSI Press Release) Human Genome Sciences Completes Patient
Enrollment in a Phase 2 Clinical Trial of HGS-ETR1 for the
Treatment
of Colorectal Cancer. February 23, 2005.
7. Humphreys, RC. Development and evaluation of cancer
therapeutic
agents targeting TRAIL receptor 1 and 2. Cancer Drug
Discovery and
Development: The Oncogenomics Handbook (Ed.: La Rochelle
WJ and
Shimkets RA, Humana Press, 2005).
8. Younes A, et al. Activity of selective agonistic monoclonal
antibodies to TRAIL death receptors R1 and R2 in primary and
cultured
tumor cells of lymphoid origin. 9th International
Conference on
Malignant Lymphoma, 2005. Oral presentation.
9. Pacey S, et al. Phase 1 and pharmacokinetic study of HGS-
ETR2, a
human monoclonal antibody to TRAIL-R2, in patients with
advanced solid
malignancies. 2005 Annual Meeting of the American Society
of Clinical
Oncology (ASCO), Orlando, Florida. Abstract #3055.
10. Hotte SJ, et al. HGS-ETR1, a fully human monoclonal
antibody to the
tumor necrosis factor-related apoptosis-inducing ligand
receptor 1
(TRAIL-R1) in patients with advanced solid cancer: results
of a Phase
1 trial. 2005 Annual Meeting of the American Society of
Clinical
Oncology (ASCO), Orlando, Florida. Abstract #3052.
11. (HGSI Press Release) Human Genome Sciences Reports Results
of Phase 1
Clinical Trials of HGS-ETR2 and HGS-ETR1 in Patients with
Advanced
Solid Tumors. May 17, 2005.
12. Tolcher, et al. A Phase 1 clinical trial of HGS-ETR2, a
fully human
monoclonal antibody to TRAIL-R2 in patients with advanced
solid
tumors. 96th Annual Meeting of the American Association for
Cancer
Research, Anaheim, California, 2005. Abstract #543.
13. Mita M, et al. A Phase 1, pharmacokinetic (PK) study of HGS-
ETR1, an
agonistic monoclonal antibody to TRAIL-R1, in patients with
advanced
solid tumors. 96th Annual Meeting of the American
Association for
Cancer Research, Anaheim, California, 2005. Abstract #544.
14. (HGSI Press Release) Human Genome Sciences Reports Results
of Phase 1
Clinical Trial of HGS-ETR1 in Patients with Advanced Solid
Tumors.
April 18, 2005.
15. Halpern W, et al. Variable distribution of TRAIL Receptor 1
in
primary human tumor and normal tissues. 16th EORTC-NCI-AACR
Symposium
on Molecular Targets and Cancer Therapeutics, 2004:
Abstract #225.
16. Humphreys R, et al. HGS-TR2J, a human, agonistic, TRAIL
Receptor-2
monoclonal antibody, induces apoptosis, tumor regression and
growth
inhibition as a single agent in diverse human solid tumor
cell lines.
16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics, 2004: Abstract #204.
17. (HGSI Press Release) Human Genome Sciences Reports Results of
Preclinical Studies of TRAIL-R1 and TRAIL-R2 Agonistic Human
Monoclonal Antibodies at EORTC-NCI-AACR Symposium. October
1, 2004.
18. Georgakis GV, 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.
19. Gillotte D, Zhang Y, Poortman C, et al. Human agonistic
anti-TRAIL
receptor antibodies, HGS-ETR1 and HGS-ETR2, induce apoptosis
in
ovarian tumor lines and their activity is enhanced by taxol
and
carboplatin. Proceedings from the AACR 2004; 73:3579.
20. Humphreys R, et al. Novel, agonistic, human anti-TRAIL
receptor
monoclonal antibodies, HGS-ETR1 and HGS-ETR2, are capable of
potently
inducing tumor regression and growth inhibition as single
agents and
in combination with chemotherapeutic agents in models of
human NSCLC.
AACR-NCI-EORTC International Conference on Molecular Targets
and
Cancer Therapeutics. November 2003. Poster #B72.
21. Georgakis GV, Li Y, Humphreys R, et al. Activity of
selective
agonistic antibodies to TRAIL death receptors R1 and R2 in
primary and
cultured tumor cells of hematologic origin. Blood
2003;102:228a
(abstract #799).
22. Johnson RL, Huang X, Fiscella M. Human agonistic anti-TRAIL
antibodies, HGS-ETR1 and HGS-ETR2, induce apoptosis in
diverse
hematological tumor lines. Blood 2003;102:981a (abstract
#3316).
23. Younes A, Kadin ME. Emerging applications for the tumor
necrosis
factor family of ligands and receptors in cancer therapy. J
Clin
Oncol 2003;21:3526-3534.
24. Pukac L, Kanakaraj P, Alderson R, et al. TRAIL-R1 mAb, a
human
agonistic monoclonal antibody to tumor necrosis factor-
related
apoptosis-inducing ligand receptor 1, induces apoptosis in
human tumor
cells in vitro and in vivo. American Association for Cancer
Research
94th Annual Meeting. July 2003, Abstract 6429.
25. Salcedo, Alderson R, Basu, et al. TRM-1, a fully human
TRAIL-R1
agonistic monoclonal antibody, displays in vitro and in vivo
anti-
tumor activity. American Association for Cancer Research
93rd Annual
Meeting. April 2002, Abstract #4240.
26. Humphreys R, et al. TRAIL-R1 and TRAIL-R2 human agonistic
monoclonal
antibodies display in vitro and in vivo activity on human
cancer
cells. Society for Biological Therapy 2002; oral
presentation.
27. (HGSI Press Release) Cambridge Antibody Technology and Human
Genome
Sciences Announce Second Drug Partnership. January 8, 2002.
28. (HGSI Press Release) Human Genome Sciences Initiates Clinical
Development of New Drug for the Treatment of Cancer. August
24, 2004.
29. (HGSI Press Release) Human Genome Sciences Announces Joint
Development
of Antibody for the Treatment of Cancer with Kirin.
December 3, 2002.
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