Human Genome Sciences Advances Anti-Cancer Drug to Phase 2 Clinical Development
Wednesday September 8, 8:15 am ET
Dosing of Patients Begins in Phase 2 Clinical Trial of HGS-ETR1
First in a Series of Phase 2 Trials of the Agonistic Human Monoclonal Antibody to TRAIL Receptor 1
ROCKVILLE, Md., Sept. 8 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - News) announced today that it has begun dosing 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 Phase 2 clinical trial is a multi-center, open-label, single-arm study to evaluate the efficacy, safety and tolerability of HGS-ETR1 in patients with relapsed or refractory non-small cell lung cancer. The Phase 2 clinical trial will be conducted in the United States, and will enroll a maximum of thirty patients. Each patient will receive four 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. Disease response will be assessed using the RECIST Criteria (Response Evaluation Criteria in Solid Tumors), which were established in 2000 to codify objective means for evaluating changing disease status and the efficacy of drugs in the treatment of solid tumors.(1) 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.
Human Genome Sciences also announced that it has begun to dose patients in an open-label, dose-escalation Phase 1b clinical trial of HGS-ETR1 to evaluate its safety and tolerability in combination with paclitaxel and carboplatin in patients with advanced solid malignancies.
F. Anthony Greco, M.D., a clinical investigator and Medical Director of The Sarah Cannon Cancer Center, Nashville, said, "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.(2) It is the leading cause of cancer death in this country in both men and women. Non-small cell lung cancers account for approximately 75-80 percent of all lung cancers.(2) Less than half of newly diagnosed patients are candidates for surgery. The majority of patients present with incurable locally advanced or metastatic disease.(3) Non-small cell lung cancer represents a significant medical need, for which further therapeutic advances will depend on the development of new agents directed at newly defined targets. This reality underlies the current 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 exploring the potential of HGS-ETR1 in Phase 2 clinical trials in patients with this deadly disease."
David C. Stump, M.D., Executive Vice President, Drug Development, said, "Based on strong preclinical evidence and the encouraging interim clinical results available to date from our ongoing Phase 1 clinical trials, we are pleased to advance HGS-ETR1 to a Phase 2 clinical trial in patients with relapsed or refractory non-small cell lung cancer. We plan in 2004 to advance HGS-ETR1 to additional Phase 2 clinical trials, and we also are initiating Phase 1b clinical studies of HGS-ETR1 in combination with chemotherapy. These are important steps forward as we continue to elucidate the potential role of HGS-ETR1 in the treatment of a number of solid tumor and other malignancies."
Craig A. Rosen, Ph.D., President, Research and Development, said, "Our own preclinical research, along with published results in the scientific literature, demonstrates 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.(4-17) Our own in vitro and in vivo preclinical studies show that HGS-ETR1 inhibits or reduces tumor growth in xenograft models of non-small cell lung cancer, and can induce significant tumor regression in some models of the disease.(9-11, 14-16) Our studies also show that the activity of HGS-ETR1 in such models may be increased by co-treatment with chemotherapeutic agents, including taxane and platinum-based agents.(6-8) One of the key milestones set by Human Genome Sciences at the beginning of this year was the advancement of HGS-ETR1 to Phase 2 clinical trials. We are pleased to have achieved that milestone, and look forward to the continuing clinical development of HGS-ETR1 for the treatment of cancer."
Interim results of two ongoing Phase 1 multi-center, open-label, dose- escalation clinical trials of HGS-ETR1 were presented at the June 2004 Annual Meeting of the American Society of Clinical Oncology (ASCO).(18-20) The data presented at ASCO 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. In a Phase 1 study conducted in patients with advanced solid tumors, thirty-three of thirty-seven patients treated to date had received prior chemotherapy. The median number of treatment regimens previously experienced was two, and ranged as high as nine. 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. The Maximum Tolerated Dose (MTD) has not been reached, and accrual in the trial continues. Plasma concentrations were observed to be in a range associated with preclinical evidence of biological activity. Durable stable disease for greater than six months was observed in one patient with metastatic sarcoma.(18, 20) In a second Phase 1 study conducted in patients with advanced solid tumors or non- Hodgkin's lymphoma, all twenty of the patients treated to date were admitted to the trial with relapsed or refractory disease, and had received prior anti- cancer treatments (chemotherapy, radiotherapy, or hormone therapy). Results presented from the ongoing clinical trial demonstrate that HGS-ETR1 is well tolerated with no clearly attributable toxicities and that the MTD has not been reached. Stable disease has been observed in five patients. The trial continues to enroll patients.(19-20)
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. The TRAIL Receptor 1 agonistic human monoclonal antibody, HGS-ETR1, was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.(21) 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.
For more information about HGS-ETR1, 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 (301) 610-5790, extension 3550. |
