Human Genome Sciences, Inc. (HGSI) has completed the enrolment and initial dosing of patients in a randomized phase 2 trial of HGS-ETR1 (mapatumumab) in combination with the chemotherapy agents paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC).
"There is an urgent medical need for effective treatment options for non-small cell lung cancer because current treatment strategies have only a minimal impact on survival," said Joachim von Pawel, M.D., a principal investigator in the study from the Asklepios Fachkliniken München-Gauting, Germany. "The majority of patients who are newly diagnosed with non-small cell lung cancer have locally advanced or metastatic disease that is currently incurable. We look forward to evaluating the potential of mapatumumab plus chemotherapy to offer a new approach to the first-line treatment of this deadly disease."
The NSCLC trial is a randomized, multi-centre, open-label Phase 2 study to evaluate the efficacy and safety of HGS-ETR1 in combination with carboplatin and paclitaxel as first-line therapy in the treatment of advanced non-small cell lung cancer (Stage IIIB or IV). 111 patients have been randomly assigned to one of three treatment groups and treated with either the two-agent combination of carboplatin and paclitaxel or the three-agent combination of carboplatin, paclitaxel, and HGS-ETR1 at either 10 mg/kg or 30 mg/kg. HGS announced the initiation of the NSCLC trial In December 2007.
"A growing body of preclinical data suggests that combining HGS-ETR1 with chemotherapy agents could be an effective approach to the treatment of a number of malignancies, including non-small cell lung cancer," said Gilles Gallant, B. Pharm., Ph.D., vice president, clinical research - oOncology, HGS. "HGS-ETR1 is the most advanced of any product in development that targets the TRAIL apoptotic pathway. The NSCLC study is one of three ongoing HGS trials designed to evaluate combinations of HGS-ETR1 with chemotherapeutic agents for the treatment of specific cancers."
The HGS-ETR1 proof-of-concept phase includes three randomized trials to evaluate its potential in combination with chemotherapy for the treatment of specific cancers:
In July 2008, HGS initiated dosing in the safety lead-in to a randomized Phase 2 trial of HGS-ETR1 in combination with Nexavar (sorafenib) in patients with advanced hepatocellular cancer, which accounts for 80-90% of all liver cancers.
The company expects to have initial data available in the third quarter of 2008 from a randomized Phase 2 trial of HGS-ETR1 in combination with Velcade (bortezomib) in advanced multiple myeloma. Patients in the multiple myeloma study will continue on treatment until the progression of disease.
These three trials, taken together, will support a decision on whether to advance HGS-ETR1 to Phase 3 development. It also is possible that a sufficiently positive result from any one of the trials could lead to a Phase 3 decision for that specific indication.
HGS-ETR1 (mapatumumab) is an agonistic human monoclonal antibody that directly induces cancer-cell death by specifically binding to and activating the protein known as TRAIL receptor 1. Using genomic techniques, HGS originally identified the TRAIL receptor 1 protein. The HGS-ETR1 antibody was generated by HGS through collaboration with Cambridge Antibody Technology. HGS is developing HGS-ETR1 as a potential treatment for a broad range of cancers.