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Cell Genesys Reports Data on an Association Between Immune Response and Anti-Tumor Activity in Patients Receiving GVAX Immunotherapy for Prostate Cancer and Ipilimumab (MDX-010)

Posted on: Tuesday, 15 April 2008, 12:00 CDT

Cell Genesys, Inc. (Nasdaq:CEGE) announced today that immunological data from the ongoing Phase 1 clinical trial of GVAX immunotherapy for prostate cancer in combination with ipilimumab (MDX-010) suggest an association between an increase in T-cell immunity and anti-tumor activity as measured by a decrease in prostate-specific antigen (PSA) serum levels. These data (Abstract #2538) were presented by Saskia JAM Santegoets, Ph.D., from the Department of Medical Oncology and Pathology of Vrije Universiteit Medical Center located in Amsterdam, Netherlands, at the annual meeting of the American Association for Cancer Research (AACR) being held in San Diego, California. GVAX immunotherapy for prostate cancer is an investigational product currently in development by Cell Genesys, and ipilimumab is a fully human anti-CTLA-4 antibody, an investigational product currently in development by Medarex, Inc. in partnership with Bristol-Myers Squibb Company.

The data presented are based on an analysis of blood samples from the first 12 patients involved in the dose escalation portion of the Phase 1 combination trial. The samples were collected from each patient prior to dosing and then at monthly intervals following the initiation of dosing. Researchers analyzed the samples to determine the potential impact of the combination regimen on T-cells, dendritic cells and antibody response. An association was observed between the dose-dependent increase in T-cell activation and decreases in PSA levels. Patients receiving the three highest doses of ipilimumab in combination with GVAX immunotherapy showed an increase in the percentage of memory T-cells as measured through peripheral blood T-cell monitoring. Patients receiving the two highest doses of ipilimumab in combination with GVAX immunotherapy had an increase in HLA-DR on T-cells, indicating T-cell activation. Additionally, researchers observed an increase in activated dendritic cells as indicated by the activation marker, CD40. No anti-PSA antibodies were detected in any of the 12 patients.

"These data presented today affirm that GVAX immunotherapy for prostate cancer used in combination with ipilimumab induces a cellular immune response and that the immune response may be associated with durable objective PSA responses, which we previously reported in June 2007 for the first 12 patients treated in this trial," said Peter K. Working, Ph.D., senior vice president, Research and Development. "We look forward to presenting updated results from this trial at the 2008 American Society of Clinical Oncology (ASCO) annual meeting, including preliminary results for the 16 additional patients who have been enrolled in the expansion cohort of the trial."

The Phase 1 trial reported on today was designed to evaluate safety and to determine a maximum tolerated dose of ipilimumab when used in combination with GVAX immunotherapy for prostate cancer. To date, 28 men with metastatic hormone refractory prostate cancer (HRPC) have been enrolled in the trial, including 12 patients in the dose escalation cohort and 16 patients in the expansion cohort. Efficacy endpoints include time to clinical disease progression, time to PSA progression and PSA response, immune response to GVAX immunotherapy, reduction in metabolic bone activity and survival. The dose of GVAX immunotherapy for prostate cancer used in this combination trial is comparable to that currently being evaluated in Cell Genesys' ongoing Phase 3 program. In the escalation phase of the trial, four doses of ipilimumab were evaluated, including 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 5 mg/kg.

As previously reported at the June 2007 ASCO meeting, investigators presented follow-up data for the first 12 patients treated in this Phase 1 clinical trial of GVAX immunotherapy for prostate cancer used in combination with ipilimumab. These data indicate that five of the six patients who received the two highest doses of antibody experienced PSA declines of greater than 50 percent, which in four patients were maintained for at least six months. In addition, four of these six patients had clinical responses, as measured by bone scan, abdominal CAT scan and bone pain. As previously reported, the five patients with PSA declines of greater than 50 percent experienced either Grade 2 or 3 immune-mediated endocrine deficiencies similar in type to those previously reported with ipilimumab administration, and were successfully treated with standard hormone replacement therapy. One patient who received the 5 mg/kg dose of ipilimumab developed a Grade 3 dose-limiting pulmonary alveolitis that responded to steroid treatment. The induction of patient-specific antibody immune responses to a broad array of previously identified cancer-associated antigens, including PSMA, NY-ESO-1 and filamin-B was also observed. These latter results are consistent with those of similar analyses from a separate study carried out in patients who received GVAX immunotherapy alone for prostate cancer in a Phase 2 trial as recently reported at the February 2008 ASCO Symposium on Genitourinary Cancer. Those data indicated that GVAX immunotherapy for prostate induced a broad array of patient-specific antibody responses that were in certain cases associated with increased patient survival.

About GVAX Immunotherapy for Prostate Cancer

GVAX immunotherapy for prostate cancer is a whole-cell, non patient-specific product designed to present the immune system with a broad spectrum of tumor antigens and stimulate an immune response against the patient's tumor. GVAX immunotherapy for prostate cancer is comprised of two prostate tumor cell lines that have been modified to secrete GM-CSF (granulocyte-macrophage colony-stimulating factor), an immune stimulatory protein that plays a key role in stimulating the body's immune response, and then irradiated for safety. Cell Genesys, in partnership with Takeda Pharmaceutical Company Limited, is currently evaluating GVAX immunotherapy for prostate cancer in two Phase 3 clinical trials, VITAL-1 and VITAL-2, for the treatment of advanced stage, hormone-refractory prostate cancer. In 2007, the VITAL-1 trial completed enrollment with 626 patients and in January 2008, Cell Genesys announced that the Independent Data Monitoring Committee (IDMC) had completed a pre-planned interim analysis for VITAL-1 and recommended that the study continue. The company currently estimates that there will be sufficient events to trigger the final analysis for VITAL-1 in the second half of 2009. Patients are continuing to be enrolled in the VITAL-2 trial at approximately 100 clinical trial sites located in North America and Europe. Cell Genesys is targeting the completion of enrollment for VITAL-2 with approximately 600 patients in the first half of 2009 and expects that there will be sufficient events to trigger the pre-planned interim analysis in the same time frame. GVAX immunotherapy for prostate cancer is currently being manufactured in Cell Genesys' bioreactor manufacturing facility, a facility that is capable of producing the product during commercialization.

About Ipilimumab (MDX-010)

Ipilimumab, also known as MDX-010, is a fully human antibody that binds CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells. Ipilimumab is being developed through a joint partnership between Medarex and Bristol-Myers Squibb. The two companies are pursuing a broad clinical development program with ipilimumab evaluating its potential use in advanced melanoma, as well as prostate, lung, pancreatic, bladder, breast, lymphoma and leukemia cancers. More than 2,000 patients have been treated with ipilimumab as a monotherapy or in combination with other agents in clinical trials. Further information regarding the ipilimumab program can be found in Medarex's public disclosure filings with the U.S. Securities and Exchange Commission (SEC).

About Cell Genesys

Cell Genesys is focused on the development and commercialization of novel biological therapies for patients with cancer. The company is currently pursuing two clinical stage product platforms--GVAX® cancer immunotherapies and oncolytic virus therapies. Ongoing clinical trials include Phase 3 trials of GVAX immunotherapy for prostate cancer, which is being developed in partnership with Takeda Pharmaceutical Company Limited, Phase 2 trials of GVAX immunotherapies for pancreatic cancer and for leukemia, and a Phase 1 trial of CG0070 oncolytic virus therapy for bladder cancer. Cell Genesys continues to hold an equity interest in its former subsidiary, Ceregene, Inc., which is developing gene therapies for neurodegenerative disorders. Cell Genesys is headquartered in South San Francisco, CA and has its principal manufacturing operation in Hayward, CA. For additional information, please visit the company's website at www.cellgenesys.com.

Forward-Looking Statement

Statements made herein about the company, other than statements of historical fact, including statements about the progress, results, findings and timing of the company's clinical trials and preclinical programs and the nature of product pipelines are forward-looking statements and are subject to a number of uncertainties that could cause actual results to differ materially from the statements made, including risks associated with the success of clinical trials and research and development programs, the regulatory approval process for clinical trials, competitive technologies and products, patents, continuation of corporate partnerships and the need for additional financings. For information about these and other risks which may affect Cell Genesys, please see the company's reports on Form 10-Q, 10-K, and 8-K and other reports filed from time to time with the Securities and Exchange Commission. The company assumes no obligation to update the forward-looking information in this press release.

Source: Business Wire

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