Geron Initiates Clinical Trial of Telomerase Cancer Vaccine in Patients with Acute Myelogenous Leukemia
Geron Initiates Clinical Trial of Telomerase Cancer Vaccine in Patients with
Acute Myelogenous Leukemia
Study Builds on Positive Data Previously Generated in Metastatic Prostate Cancer
Patients Protocol Under Geron's IND is First to Employ Prime-Boost Regimen to
Extend Duration of Telomerase Immunity
MENLO PARK, Calif., Jul 11, 2007 (BUSINESS WIRE) -- Geron Corporation (GERN)
announced today the initiation of a clinical trial of its telomerase cancer
vaccine, GRNVAC1, in patients with acute myelogenous leukemia (AML) in complete
remission.
The vaccine is produced from a patient's blood using a unique process that
generates highly activated dendritic cells (DC) that contain RNA coding for the
protein component of telomerase. This new approach to cancer immunotherapy has
been clinically shown to safely generate high levels of cytotoxic lymphocytes
that kill telomerase positive cancer cells after as few as six weekly injections
into the skin.
The primary objective of this new Phase I/II study is to evaluate the safety and
feasibility of a prime-boost vaccination regimen that extends the duration of
telomerase immunity. Secondary objectives are to evaluate the immune response to
GRNVAC1 and to explore the effects of vaccination on minimal residual disease and
relapse rates. A total of six sites in the United States are planned to
participate in this multi-center trial.
"AML is an appropriate indication for investigating a cancer immunotherapy that
targets telomerase because of high telomerase expression in AML cells, the great
unmet clinical need, especially in older patients who frequently relapse after
chemotherapy, and the low tumor burden after consolidation chemotherapy," said
John DiPersio, M.D., Ph.D., chief of the Division of Oncology and deputy director
of the Siteman Cancer Center at Washington University School of Medicine, St.
Louis, who is the study's lead investigator. "Patients at high risk of relapse
are in need of additional therapies that are well tolerated. This study is an
important step in understanding the role that immunotherapy directed against
telomerase might play in cancer treatment."
Alan Colowick, M.D., Geron's president, oncology, said, "We are excited to begin
this multi-center study in AML patients who have a high risk for relapse. A great
deal of work has enabled us to apply and extend the initial clinical findings for
GRNVAC1 in prostate cancer to AML patients. We have scaled and modified the
manufacturing of the vaccine to enable a multi-site design with central
manufacturing. In addition, we have optimized the prime-boost regimen to enhance
the duration of immunity to telomerase in previous clinical studies, and we have
demonstrated successful ex vivo DC activation and loading with telomerase antigen
in samples taken from patients with AML. We look forward to investigating the
tolerability and potential clinical utility of GRNVAC1 in patients with AML."
AML is the most common form of acute leukemia in adults. Although present in all
age groups, AML is most often diagnosed in adults over the age of 60. The
American Cancer Society estimates that there were more than 11,900 new cases of
AML in 2006 in the United States. With current standard chemotherapy regimens,
estimates of five-year survival are 25% to 30% for adults younger than 60. Fewer
than 10% of older patients with AML attain long-term survival.
GRNVAC1 is an immunotherapeutic product made from autologous dendritic cells
transfected with mRNA encoding telomerase protein and the lysosomal targeting
signal, lysosome-associated membrane protein (LAMP). This autologous product is
designed to induce cellular immune responses to telomerase, an antigen highly
expressed in the nucleus of cancer cells and found on their surface but not
expressed in most normal cells. Unlike other tumor targets, hTERT, the protein
component of telomerase, is essential for maintaining the proliferative capacity
and survival of the majority of tumor cell types.
Researchers at Duke University, in collaboration with Geron, have conducted both
preclinical and clinical studies using a vaccine product comparable to GRNVAC1.
In Vitro Studies
In vitro studies have demonstrated that autologous dendritic cells transfected
with hTERT mRNA stimulate hTERT-specific cytotoxic T-cells (CTL) from the
peripheral blood of patients with cancer. These studies have also shown that DC
transfected with hTERT mRNA containing the sequence for LAMP may further enhance
the efficacy of this approach by optimally stimulating CD8+ and CD4+ T-cell
responses (Nair et al, Nat. Med. 2000;6(9):1011-1017) (Su et al, Cancer Res.
2002;62(17):5041-5048).
Clinical Studies
The results of the first study testing hTERT-LAMP mRNA-transfected DC in
metastatic prostate cancer patients were published in the Journal of Immunology
(Su et al, J. Immunol. 2005;174(6):3798-807). In this study, 20 patients were
enrolled and randomized to receive either hTERT mRNA-transfected DC (11 patients)
or hTERT-LAMP mRNA-transfected DC (9 patients). Treatment was well tolerated. In
19 of 20 patients, expansion of hTERT-specific T-cells in the peripheral blood of
patients was measured after vaccination, with 0.9% to 1.8% of circulating T-cells
exhibiting anti-telomerase activity. Patients immunized with the chimeric
hTERT-LAMP vaccine exhibited slightly stronger T-cell, and particularly CD4+
T-cell, immune responses to telomerase compared to patients immunized with the
unmodified hTERT mRNA-transfected DC vaccine. Moreover, hTERT-specific T-cell
killing was enhanced in subjects receiving hTERT-LAMP, suggesting that the
improved CD4+ response can augment a CTL response.
Three other Phase I optimization studies of hTERT-LAMP mRNA-transfected DC were
conducted at Duke University in patients with metastatic prostate cancer, renal
cell carcinoma and hematologic malignancies. Approximately 45 cancer subjects
have been treated to date under the Duke protocols. Vaccine-related toxicities
were primarily Grade 1-2. Overall, the adverse event pattern in these studies
included non-specific, disease-related effects and skin reactions consistent with
delayed type hypersensitivity (DTH).
Geron is developing first-in-class biopharmaceuticals for the treatment of cancer
and chronic degenerative diseases, including spinal cord injury, heart failure,
diabetes and HIV/AIDS. The company is advancing an anti-cancer drug and a cancer
vaccine that target the enzyme telomerase through multiple clinical trials. Geron
is also the world leader in the development of human embryonic stem cell-based
therapeutics, with its spinal cord injury treatment anticipated to be the first
product to enter clinical development. For more information, visit
geron.com.
This news release may contain forward-looking statements made pursuant to the
"safe harbor" provisions of the Private Securities Litigation Reform Act of 1995.
Investors are cautioned that such forward-looking statements in this press
release regarding potential applications of GRNVAC1 and Geron's telomerase
technology constitute forward-looking statements that involve risks and
uncertainties, including, without limitation, risks inherent in the development
and commercialization of potential products, uncertainty of clinical trial
results or regulatory approvals or clearances, need for future capital,
dependence upon collaborators and maintenance of our intellectual property
rights. Actual results may differ materially from the results anticipated in
these forward-looking statements. Additional information on potential factors
that could affect our results and other risks and uncertainties are detailed from
time to time in Geron's periodic reports, including the quarterly report on Form
10-Q for the quarter ended March 31, 2007.
SOURCE: Geron Corporation
Geron Corporation
David L. Greenwood, 650-473-7765
Chief Financial Officer
info@geron.com
or
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