Northwest Biotherapeutics Conducts Ovarian Cancer Clinical Trial
Northwest Biotherapeuticsannounced that a Phase I/II clinical trial in at least 30 patients, using DCVax-L for recurrent ovarian cancer, has begun at The University of Pennsylvania Center for Research on Early Detection and Cure of Ovarian Cancer and the Abramson Cancer Center. The first patients have been enrolled and have undergone initial treatment steps in preparation for receiving DCVax-L.
The trial involves two sequential studies, and comprises an innovative combination of multiple treatment modalities. DCVax-L forms the cornerstone of the treatment regimen, and is complemented by administration of low doses of certain existing approved drugs to help improve the immune system environment, as well as by adoptive transfer of patients' DCVax-L primed T cells. The principal investigators for the trial are Dr. George Coukos and Dr. Sarah Kim, and the Penn Investigational New Drug ("IND") sponsor is Dr. Carl June. The funding is being provided by the Ovarian Cancer Vaccine Initiative. (See below for more information about this Initiative.)
DCVax-L is a personalized immunotherapy for cancer, which is made from a patient's own dendritic cells (the master cells which initiate and manage the overall immune system response to a disease), and the "antigens" (biomarkers) from the patient's own tumor tissue which has been surgically removed as part of the standard of care. Such immunotherapy is sometimes referred to as a "therapeutic vaccine," as it is designed not to prevent cancer but to treat patients who already have cancer.
In the first study being conducted by NWBT and Penn, patients will first undergo standard surgery to reduce their tumor burden. Patients will then receive limited doses of two existing drugs to improve the immune system environment and modify the tumor vasculature. Cancer researchers have become increasingly focused on the role of tumor vasculature and the tumor microenvironment, as well as the possible role of a certain kind of cells called "regulatory T cells," in causing a patient's immune system to become unresponsive to the patient's tumor, and on the potential importance of modifying these factors in order to achieve robust and durable immune responses against tumors.
Following the preparatory treatments, the patients in this ovarian cancer trial will receive a series of three immunizations with DCVax-L, each two weeks apart, while continuing to receive the low doses of two drugs intended to keep the immune system and the tumor microenvironment in a beneficial condition.
The second study, which will be a follow-on to the first study but covered by a separate IND filing, will compare two treatment arms continuing further with the drug and DCVax-L regimen, and adding the adoptive transfer of DCVax-L primed, and expanded T cells.
By combining multiple diverse treatment modalities, structured around DCVax-L as the cornerstone, this clinical trial is designed to implement evolving research findings on the complex interactions between tumors and the "host" tissues in patients, and evolving findings on the many facets of the immune system and what may be required for effective anti-tumor responses.
The trial is also designed to minimize any potential toxicity for patients. Clinical trial experience to date with DCVax-L products in over 100 treatment cycles in brain cancer patients has shown no toxicity from the DCVax-L treatment (no grade 3 or 4 adverse events). This multi-modal ovarian cancer trial has been designed to maintain this minimal-toxicity approach, by using only low doses of the two drugs complementing DCVax-L for preparatory effects.
The first patients have been enrolled in the study by Dr. George Coukos. Dr. Coukos stated, "this is a very significant event for patients at the University of Pennsylvania and nationwide who are diagnosed with ovarian cancer. We are excited to work with Northwest Biotherapeutics on this cutting edge clinical trial, and to test the DCVax platform on an additional cancer that carries a poor prognosis."
Dr. Carl June, the Penn sponsor on the trial, stated, "the combination of DCVax-L for ovarian cancer with adoptive immunotherapy using T cells primed by DCVax-L is an innovative approach that deserves testing in clinical trials."
"We are very pleased to add Ovarian cancer to the DCVax platform, and to have Dr. George Coukos and Dr. Carl June lead this effort as the principal investigators for this clinical trial," stated Alton Boynton, President and Chief Executive Officer of Northwest Biotherapeutics. "Drs. Coukos and June are world renowned experts in immunotherapy and in ovarian cancer. They are playing a major role in the pioneering of novel cancer treatment strategies -- particularly by combining multiple different therapeutic approaches."
Ovarian cancer is the fourth leading cause of cancer death among women in the U.S. Approximately 22,400 new cases were diagnosed in the U.S. in 2006, and about 15,300 deaths occurred. In the majority of ovarian cancer cases, the disease has already reached late stage, and spread beyond the ovaries, before it is detected and diagnosed. After initial surgical removal of tumors, and treatment with currently available drugs, the median time to disease recurrence is 18 to 20 months. Recurrent disease is considered incurable and usually results in death, even with aggressive chemotherapy treatments. Accordingly, there is a major unmet medical need for new and more effective treatments for ovarian cancer -- especially recurrent ovarian cancer.
The DCVax platform uses a patient's own tumor, surgically removed as part of the standard of care, to prepare a mix of their personal cancer biomarkers. These personal cancer biomarkers are then loaded onto the patient's own dendritic cells (the master cells responsible for starting and managing the body's overall immune response), and injected back into the patient through a simple intra-dermal injection, similar to an insulin shot, at various intervals over a period of up to three years.