Seattle Genetics initiates PI trial of Hodgkin's disease therapy
investigating the viability of a treatment for Hodgkin's disease
and other CD30-positive haematologic malignancies.
The biotechnology company have been active within the Lymphoma field having devoted considerable resources into developing monoclonal antibody-based therapies for the treatment cancers, including non-Hodgkin's lymphoma, multiple myeloma, acute myeloid leukaemia and Hodgkin's disease.
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. The lymphomas are divided into two major categories: Hodgkin's disease and all other lymphomas, or non-Hodgkin's lymphomas.
Hodgkin's disease is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. A defining attribute of the Reed-Sternberg cell is its expression of the CD30 antigen.
According to the American Cancer Society, an estimated 7,800 cases of Hodgkin's disease will be diagnosed in the United States during 2006, and nearly 1,500 people will die of the disease.
The American Cancer Society estimates that nearly 59,000 new cases of non-Hodgkin's lymphoma will be diagnosed in the United States during 2006.
An estimated 15 per cent of non-Hodgkin's lymphomas are of T-cell origin, many of which express CD30.
Seattle Genetics' SGN-35 is an antibody-drug conjugate (ADC) that utilises Seattle Genetics' proprietary technology to empower antibodies by linking them to potent cell killing drugs.
"SGN-35 represents an exciting, emerging class of antibody-based therapeutics," commented Clay Siegall, President and Chief Executive Officer of Seattle Genetics.
"Many antibodies lack sufficient potency on their own to have a therapeutic benefit. ADCs exploit an antibody's ability to target tumour cells to deliver a highly potent drug payload, sparing non-targeted cells many of the toxic effects of traditional chemotherapy," he added.
SGN-35 becomes the first auristatin-based ADC that Seattle Genetics has advanced into clinical trials that is joined by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology.
The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalisation into CD30-expressing tumour cells, resulting in a targeted cell-killing effect.
Treatment with SGN-35 resulted in complete tumour regressions in preclinical models of Hodgkin's disease and anaplastic large cell lymphoma (ALCL).
The single-agent, dose-escalation phase I study is designed to evaluate the safety, pharmacokinetic profile and antitumour activity of SGN-35 in patients with relapsed or refractory CD30-positive haematologic malignancies, including Hodgkin's disease.
The trial is expected to enrol up to approximately 40 patients at multiple centers in the United States.
"SGN-35 has the potential to address a significant unmet clinical need in the relapsed setting of Hodgkin's disease and CD30-positive T-cell lymphomas," said Andres Forero-Torres, associate professor in the Division of Haematology-Oncology at the University of Alabama, Birmingham.
"Currently, patients and their doctors have only limited therapeutic options and no approved antibody-based treatments."
