Dynavax Technologies Corporation has announced preliminary data from an ongoing open label phase 2a study of the company's TLR9 agonist used in combination with rituximab as a treatment for patients with non-Hodgkin's lymphoma.
The results were reported this morning by Dr Jonathan W. Friedberg, M.D. of the James P. Wilmot Cancer Centre, University of Rochester, and by Dr. Arnold Freedman at the Dana-Farber Cancer Institute in Boston, Massachusetts, at the annual meeting of the American Society of Hematology in Orlando, Florida. The study was funded by the National Cancer Institute with additional support and drug supplied by Dynavax.
The study enrolled 23 follicular lymphoma patients who had relapsed after at least one prior treatment. Patients were evaluated using functional assays, gene expression profiling and immunohistochemistry studies. Dr Friedberg indicated that patients treated with the TLR9 agonist who had clearly increased expression of TLR9 agonist and interferon-inducible genes showed a prolonged time to progression as compared to patients who were less responsive to the drug and to historical controls. The combination of rituximab and the TLR9 agonist was well tolerated, and adverse events were minimal.
According to Dr Friedberg, "The data suggest that a combination immunotherapy composed of a CpG oligonucleotide (TLR9 agonist) and rituximab augments the immunological response and favourably alters the malignant microenvironment. Importantly, we demonstrated increased biological activity in several biomarkers normally associated with tumour response. Enhanced immune effects were observed in a majority of patients. In a subset of patients biopsied after therapy, there is a suggestion of direct immune effects within lymph nodes involved by the follicular lymphoma."
In preclinical models, the use of a TLR9 agonist has been shown to enhance the effect of various anticancer monoclonal antibodies. Drs. Friedberg and Freedman previously reported a phase 1, dose-escalation trial of Dynavax's TLR9 agonist in combination with rituximab in 20 patients with non-Hodgkin's lymphoma. In this trial, dose-dependent pharmacological activity was demonstrated without significant toxicity. On December 5, Dynavax announced the initiation of a phase 1 dose escalation trial in combination with a standard therapeutic regimen used to treat metastatic colorectal cancer.
Dynavax Technologies Corporation discovers, develops, and intends to commercialize innovative TLR9 agonist-based products to treat and prevent allergies, infectious diseases, cancer, and chronic inflammatory diseases using versatile, proprietary approaches that alter immune system responses in highly specific ways. Our TLR9 agonists are based on immunostimulatory sequences, or ISS, which are short DNA sequences that enhance the ability of the immune system to fight disease and control chronic inflammation. Our pipeline includes: Tolamba, a ragweed allergy immunotherapeutic, for which a major safety and efficacy trial (DARTT) is currently underway, and that is in a supportive clinical trial in ragweed allergic children, Heplisav, a hepatitis B vaccine in phase 3, a therapy for non-Hodgkin's lymphoma (NHL) in phase 2, and a therapy for metastatic colorectal cancer in phase 1. Our pre- clinical asthma and COPD programs are partnered with AstraZeneca. Funding for our colorectal cancer trial and our preclinical programs in therapies for hepatitis B and hepatitis C, and for an influenza vaccine has been provided by Symphony Dynamo, Inc. and the NIH, and these programs represent future partnering opportunities.