The randomized, multi-center Phase II trial was conducted by the Eastern Cooperative Oncology Group (ECOG), an organization of leading cancer research institutions, and was sponsored by Therion Biologics Corporation. The study's principal investigator, Howard Kaufman, M.D., Director of the Tumor Immunotherapy Program at Columbia University, presented results from Abstract #12 at the 2002 American Society of Clinical Oncology (ASCO) meeting on Sunday, May 19th at 2:30 pm. Playback of the oral presentation also is available for viewing at www.asco.org.
"Prostate cancer patients with early metastatic disease face difficult treatment decisions. Current clinical options include hormone ablation therapy or a 'watch and wait' approach, which can have serious physical or emotional side effects," stated Dr. Kaufman. "The data presented here introduce a potential therapeutic alternative for these patients using Therion's pox virus vaccines."
Dr. Kaufman added, "Based on historical statistics, we anticipated that a majority of our Phase II patients would experience PSA progression or relapse within six months. Instead, all study participants receiving pox virus vaccines have shown delayed PSA and clinical progression to date. In addition, less than 50% of prime-boost treatment group has rising PSA levels after 24 months. We believe this is extremely compelling data that warrants further evaluation of the prime-boost PSA vaccine approach in larger, appropriately controlled clinical trials."
"These Phase II results support and improve upon earlier findings from Therion's Phase I trial of PROSTVAC. In that first clinical study, 42% of early metastatic prostate cancer patients remained PSA-progression free for six months or more following treatment with a single component of the PROSTVAC vaccine," said Jeff Edelson, M.D., Senior Vice President, Clinical Development and Chief Medical Officer at Therion Biologics. "Together these data provide pharmaceutical proof of concept for our PSA-based pox virus vaccines, reinforcing the safety, demonstrating the likely clinical benefit and supporting the decision to move into pivotal Phase III clinical trials of PROSTVAC-VF."
ECOG Phase II Study Details
The randomized Phase II study enrolled 70 prostate cancer patients who had undergone surgery or radiation treatment to remove primary prostate tumors. Following tumor removal, all study subjects exhibited rising PSA levels but no evidence of metastatic disease. Patients were randomized into separate study groups to evaluate three different vaccination regimens. Each group received one of the following treatment regimens:
Group A received four doses of fowlpox-PROSTVAC (FFFF),
Group B received three doses of fowlpox-PROSTVAC followed by one dose of vaccinia-PROSTVAC (FFFV), or
Group C received one dose of vaccinia-PROSTVAC followed by three doses of fowlpox-PROSTVAC (VFFF).
The Phase II study endpoints included safety and tolerability of the PROSTVAC vaccines and evaluation of PSA levels, an indicator that typically correlates with tumor recurrence. In addition, investigators examined clinical evidence of metastatic disease.
Data evaluated at 24 months post treatment show reduced time to PSA progression in all study arms and indicate a strong positive trend in favor of a prime boost regimen (VFFF). The median time to PSA progression was 13.6 months, 9.3 months and not yet reached in groups A, B, and C, respectively. Sixty-two percent of patients receiving the prime boost regimen (group C) were PSA progression free at 24 months. In addition, 78% of total Phase II patients remained free of tumor metastases. Side effects were minor and included swelling at injection site and low-grade fever.
"This trial is emblematic of Therion's clinical strategy to expand our body of knowledge throughout our product development programs, thereby increasing the probability of success in future large-scale trials," said Mark Leuchtenberger, President and Chief Executive Officer of Therion. "Moving forward, we will leverage our clinical experience with TRICOM�, a combination of three co-stimulatory molecules, to further optimize PROSTVAC-VF and finalize our lead product candidate for evaluation in Phase III clinical trials. Registration studies for PROSTVAC-VF/TRICOM will employ the same prime boost protocol used in ECOG group C, the treatment arm that responded most favorably to vaccination."
The TRICOM component of Therion's next generation PSA vaccine is designed to optimize antigen presentation and activation of cytotoxic T cells critical for tumor destruction. Together, this combined vaccine is anticipated to further strengthen the immune system's defenses against PSA-bearing prostate cancers. Therion has already incorporated TRICOM into its development program for colorectal cancer and other CEA-bearing tumors. The program's lead investigator, Dr. John Marshall of Georgetown University, will report at ASCO strong safety profiles and encouraging anecdotal responses in clinical studies of CEA-TRICOM.
Background on PROSTVAC Vaccines
PROSTVAC-VF is a recombinant vaccine that targets prostate-specific antigen (PSA), a protein produced by prostate tumor cells. Circulating PSA levels serve as a marker of disease progression. Therion's PROSTVAC-VF product consists of two components, vaccinia-PSA (V), which is designed to "prime" or generate an initial immune response against cells displaying PSA, and fowlpox-PSA (F), which is administered subsequently as a booster to enhance and sustain the immune response. Development of this and other Therion vaccines is supported by a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute.
About Therion Biologics
Therion Biologics Corporation is focused on the development of therapeutic vaccines for cancer and preventive vaccines for AIDS. Therion's most advanced product, PROSTVAC-VF, is currently in Phase II studies for prostate cancer. Under the terms of a strategic collaboration with Aventis Pasteur, a second product, ALVAC-CEA/B7.1, will move into pivotal clinical trials in the next two years for colorectal cancer. The company also has a broad pipeline of vaccines in early clinical development for treatment of major cancers, including breast cancer, melanoma and other solid tumors. In addition to Aventis, Therion's partners include the National Cancer Institute and a network of leading clinical institutions around the world. Therion is headquartered in Cambridge, Massachusetts.
