Mapatumumab :TRAIL receptor 1 Agonistic Human Monoclonal Antibody for Advanced Non-Hodgkin's Lymphoma Reaches Phase 2 Trial
Mar 4, 2005, 09:37, Reviewed by: Dr.
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"This therapeutic approach produces cures in approximately fifty percent of patients with aggressive lymphoma. Additional chemotherapeutic and other therapeutic modalities are used to treat non-Hodgkin's lymphoma patients who relapse or do not respond, but cures are difficult to achieve."
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By Akanksha, Pharmacology Correspondent,
Human Genome Sciences, Inc.announced today that it has completed the enrollment and initial dosing of patients in a Phase 2 clinical trial of HGS-ETR1 (mapatumumab) in advanced non-Hodgkin's lymphoma.
The Phase 2 clinical trial is a multi-center, open-label study to evaluate the efficacy, safety and tolerability of HGS-ETR1, an agonistic human monoclonal antibody to TRAIL receptor 1, in patients with relapsed or refractory non-Hodgkin's lymphoma.
Patients enrolled in the trial are receiving up to six cycles of treatment in the absence of disease progression, with HGS-ETR1 administered as an intravenous infusion once every twenty-one days.
The objectives of the study are to evaluate disease activity and tumor response to HGS-ETR1 in patients with advanced non-Hodgkin's lymphoma, to evaluate the safety and tolerability of HGS-ETR1, and to determine plasma concentrations of HGS-ETR1 for use in a population pharmacokinetic analysis.
On November 30, 2004, Human Genome Sciences announced the completion of enrollment and initial dosing of patients in a Phase 2 study of HGS-ETR1 in advanced non-small cell lung cancer.On February 23, 2005, the company announced the completion of enrollment and initial dosing of a Phase 2 study of the drug in advanced colorectal cancer.
The three Phase 2 studies of HGS-ETR1 initiated to date fit into a global clinical development program through which Human Genome Sciences is evaluating the novel, genomics-derived anticancer drug's potential for use in the treatment of specific cancers.
Anas Younes, M.D., Professor, Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, said, "The current standard of care for non- Hodgkin's lymphoma calls for treating most patients with a combination of chemotherapy and, in recent years, monoclonal antibodies. This therapeutic approach produces cures in approximately fifty percent of patients with aggressive lymphoma. Additional chemotherapeutic and other therapeutic modalities are used to treat non-Hodgkin's lymphoma patients who relapse or do not respond, but cures are difficult to achieve. There remains a significant need for new therapies that can improve response rates, extend the duration of response, extend survival, minimize toxicity, and provide patients with improved quality of life. We look forward to continuing the evaluation of HGS-ETR1 to determine whether it may play a role in the treatment of non- Hodgkin's lymphoma."
Gilles Gallant, B. Pharm., Ph.D., Vice President, Clinical Oncology, said, "We are pleased to have completed the enrollment and initial dosing of three Phase 2 studies to evaluate the potential use of HGS-ETR1 as a treatment for specific cancers, including non-small cell lung cancer, colorectal cancer and, now, non-Hodgkin's lymphoma. We have seen a high level of interest in the emerging clinical and preclinical evidence demonstrating that agonistic antibodies to TRAIL receptors 1 and 2 have significant potential to provide novel therapeutic options to patients with a variety of cancer types, including non-Hodgkin's lymphoma.We expect to have the results of all three of the ongoing Phase 2 studies of HGS-ETR1 available in 2005. We also have initiated Phase 1b clinical studies of HGS-ETR1 in combination with chemotherapy. We plan to continue to elucidate the potential of HGS-ETR1 as a treatment for non-Hodgkin's lymphoma and solid tumor malignancies, both as a single agent and in combination with chemotherapeutic agents."
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.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. 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. Some preliminary evidence of biological activity has been observed. Durable stable disease was observed in some patients.
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.
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. 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-Hodgkin's lymphoma is the seventh most common cancer in the United States, with approximately 56,000 new cases diagnosed each year. 
- Human Genome Sciences, Inc.
Human Genome Sciences
For more information about HGS-ETR1,check the related links .Health professionals interested in more information about trials involving Human Genome Sciences products are requested to inquire via the Contact Us section of the Human Genome Sciences web site,or by calling 301-610-5790, 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.
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