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Patient Enrollment and Initial Dosing Complete in Phase 2 Trial of HGS-ETR1

ROCKVILLE, Md., Nov. 30 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (NASDAQ:HGSI) announced today that it has completed the enrollment and initial dosing of patients in a Phase 2 clinical trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL Receptor 1) in patients with advanced non- small cell lung cancer.

The multi-center, open-label, single-arm Phase 2 clinical trial is designed to evaluate the efficacy, safety and tolerability of HGS-ETR1 in patients with relapsed or refractory non-small cell lung cancer.(1) Patients enrolled in the trial will receive 10 mg/kg doses of HGS-ETR1 administered as an intravenous infusion 21 days apart. The primary objective of the study is to evaluate tumor response. The secondary objectives are to evaluate the safety and tolerability of HGS-ETR1, and to determine plasma concentrations of HGS-ETR1 for use in a population pharmacokinetic analysis.

The Phase 2 study of HGS-ETR1 in patients with non-small cell lung cancer is the first in a series of Phase 2 clinical trials of HGS-ETR1 through which Human Genome Sciences plans to evaluate the drug's potential for use in the treatment of specific cancers. Phase 2 clinical trials of HGS-ETR1 also have been initiated in patients with colorectal cancer and in patients with non- Hodgkin's lymphoma.(2,3) In addition, Phase 1b clinical trials of HGS-ETR1 have been initiated to evaluate its safety and tolerability in combination with paclitaxel and carboplatin, and in combination with gemcitabine and cisplatin.

F. Anthony Greco, M.D., a clinical investigator and Medical Director of The Sarah Cannon Cancer Center, Nashville, said, "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.(4,5) The rapid enrollment of the current Phase 2 clinical trial of HGS-ETR1 reflects both the unmet medical need and the high level of interest in the ability of TRAIL receptor antibodies to trigger apoptosis in numerous cancer cell lines, including non-small cell lung cancer. We look forward to continuing to evaluate the potential of HGS-ETR1 in patients with this deadly disease."

David C. Stump, M.D., Executive Vice President, Drug Development, said, "We are pleased to have completed the enrollment of our Phase 2 clinical trial of HGS-ETR1 in patients with relapsed or refractory non-small cell lung cancer. Patients are currently being treated, and we expect to have results available by mid-2005. We continue to enroll patients in our Phase 2 trials of HGS-ETR1 in colorectal cancer and non-Hodgkin's lymphoma, as well as our Phase 1b clinical studies of HGS-ETR1 in combination with chemotherapy. The interim results from our ongoing Phase 1 clinical trials of HGS-ETR1 demonstrate that it is well tolerated and can be safely and repetitively administered. We believe that HGS-ETR1 has potential for use in the treatment of a broad range of solid tumor and other malignancies."

Interim results of two ongoing Phase 1 multi-center, open-label, dose- escalation clinical trials of HGS-ETR1 were presented in September 2004 at the 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland.(6-8) The data presented demonstrate the safety and tolerability of HGS-ETR1 in patients with advanced solid tumors or non- Hodgkin's lymphoma, and support further evaluation of HGS-ETR1 in Phase 2 clinical trials, both as a single agent and in combination with chemotherapy. Data were presented on 39 patients treated to date in a Phase 1 study conducted in patients with advanced solid tumors.(6,8) Interim results of the ongoing study demonstrate that HGS-ETR1 can be administered safely and repetitively to patients with advanced solid malignancies at doses up to and including 10 mg/kg intravenously every 28 days. No evidence of drug-related hematologic or hepatic toxicity has been observed at the doses administered to date. Some preliminary evidence of biological activity has been observed. Durable stable disease for greater than eight months was observed in one patient with metastatic sarcoma. Durable stable disease was observed for four months in one patient with head-and-neck cancer and in one patient with Ewing's sarcoma; both patients continue on treatment. Data also were presented on 24 patients treated to date in an additional Phase 1 study conducted in patients with advanced solid tumors or non-Hodgkin's lymphoma. Results presented from the ongoing clinical trial demonstrate that HGS-ETR1 is well tolerated with no clearly attributable toxicities to date and that the Maximum Tolerated Dose has not been reached. Stable disease has been observed in eight patients for greater than two cycles. The trial continues to enroll patients.(7-8)

Human Genome Sciences, using genomic techniques, originally identified the TRAIL Receptor-1 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 1 plays 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 the receptor and stimulate the TRAIL Receptor-1 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 1. 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.(9-25)

The TRAIL Receptor 1 agonistic human monoclonal antibody, HGS-ETR1, was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.(26) The drug will be produced in the Human Genome Sciences clinical manufacturing facilities located in Rockville, Maryland. Human Genome Sciences holds the commercial rights to the drug.

Non-small cell lung cancer accounts for approximately 75-80 percent of all lung cancers. It is expected that more than 173,000 new cases and more than 160,000 deaths of lung cancer will occur in the United States in 2004. It is currently the leading cause of cancer death in this country in both men and women.(4)

Footnotes:
1. (HGSI Press Release) Human Genome Sciences Advances Anti-Cancer Drug to Phase 2 Clinical Development. September 8, 2004.
2. (HGSI Press Release) Human Genome Sciences Initiates a Phase 2 Clinical Trial of HGS-ETR1 in Patients with Colorectal Cancer. October 13, 2004.
3. (HGSI Press Release) Human Genome Sciences Begins Dosing of Patients in a Phase 2 Clinical Trial of HGS-ETR1 in Non-Hodgkin's Lymphoma. October 13, 2004.
4. Jemal A, Tiwari RC, Murray T, et al. Cancer Statistics, 2004. Cancer 2004; 54(1):8-29.
5. 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.
6. Cohen RB, et al. "A Phase 1 Clinical Trial of HGS-ETR1, an Agonistic Monoclonal Antibody to TRAIL-R1, in Patients with Advanced Solid Tumors." 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Oral Presentation.
7. Hotte SJ, et al. Phase 1 Study of a Fully Human Monoclonal Antibody to the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 1 (TRAIL-R1) in Subjects with Advanced Solid Malignancies or Non-Hodgkin's Lymphoma (NHL). 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #208.
8. (HGSI Press Release) Human Genome Sciences Reports Results of Ongoing Phase 1 Clinical Trials of HGS-ETR1 in Patients with Advanced Cancers. September 29, 2004.
9. Tolcher AW, et al. A Phase 1 and Pharmacokinetic Study of HGS-ETR1, A Fully Human Monoclonal Antibody to TRAIL-R1 (TRM-1), in Patients with Advanced Solid Tumors. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #3060.
10. Le LH, 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. Humphreys RC, et al. 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. 94th AACR Annual Meeting. Abstract 642.
16. Alderson RF, et al. TRAIL-R2 mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis inducing ligand receptor 2, induces apoptosis in human tumor cells. 94th AACR Annual Meeting. Abstract 963.
17. Buchsbaum DJ, Zhou T, Grizzle WE, et al. Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model. Clin Cancer Research 2003; 9:3731-3741.
18. Pukac, Kanakaraj, Alderson, 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.
19. Ashkenazi A. Targeting death and decoy receptors of the tumor necrosis factor superfamily. Nat Revs Cancer 2002; 2:420-430.
20. Salcedo, Alderson, 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.
21. 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.
22. Chuntharapai A, Dodge K, Grimmer K, et al. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 2001; 166:4891-4898.
23. Ichikawa K, Liu W, Zhao L, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 2001; 7:954-960.
24. Ashkenazi A. Apo-2L/TRAIL in Cytokine Reference. Academic Press 2000.
25. Ashkenazi A. et al. Safety and anti-tumor activity of recombinant soluble APO2 ligand. J Clin Inv July 1999; 104(2): 155-162.
26. (HGSI Press Release) Cambridge Antibody Technology and Human Genome Sciences Announce Second Drug Partnership. January 8, 2002.

Source: Human Genome Sciences, Inc.

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