OXiGENE's CA4P Becomes First Vascular Targeting Agent to be Combined with Monoclonal Antibody in Human Trials
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Company's Lead Compound Enters Clinical Study in Advanced Colorectal Cancer
WALTHAM, Mass.--(BUSINESS WIRE)--Sept. 30, 2003-- OXiGENE, Inc. (NASDAQ: OXGN, XSSE: OXGN) today announced the initiation of a Phase I/II combination trial of its lead anti-cancer agent, Combretastatin A4 Prodrug (CA4P), and the iodine-labeled antibody A5B7 ((131)I-A5B7), in patients with advanced colorectal cancer. With this study, CA4P is now involved in five concurrent human oncology trials in the United States and Europe.
Approximately 35 patients are expected to be recruited for the trial, the world's first human study combining a Vascular Targeting Agent (VTA) with radioimmunotherapy (RIT). The study will be carried out at Mount Vernon and Royal Free Hospitals in the United Kingdom under the sponsorship of Cancer Research UK, the world's largest volunteer-supported cancer research organization. Among the trial's objectives: the assessment of the safety profile of the combination of (131)I-A5B7 and CA4P, the gathering of preliminary evidence of efficacy and a determination of the maximum tolerated regimen. The trial has received approval from the U.K.'s Medicines and Healthcare products Regulatory Agency.
"This study fulfills one of the key milestones we established early in 2003 - the initiation of additional clinical trials of CA4P aimed at specific cancer indications," said OXiGENE President and Chief Executive Officer Fred Driscoll. "CA4P is now being evaluated as a single agent as well as in separate combination trials with radiotherapy, chemotherapy and, now, a monoclonal antibody. These combination trials will demonstrate whether CA4P has the potential to significantly enhance the clinical benefit in a variety of approaches to cancer treatment in large disease settings."
Independent researchers funded by Cancer Research UK have studied the combination of (131)I-A5B7 and CA4P in human colorectal cancer tumors implanted in mice. Reporting their findings in a study published in the June 2001 issue of the peer-reviewed journal Cancer Research, researchers noted that combining RIT with CA4P "can convert tumor growth inhibition into tumor eradication in mice." While RIT administered alone inhibited tumor growth for approximately 35 days, after which all tumors regrew, the combination of RIT and CA4P produced a significantly greater effect: Tumors were eradicated in 85 percent of mice, with a single tumor regrowing at 97 days.
Colorectal cancer is the second leading cause of cancer-related deaths in the United States. In 2003, an estimated 57,100 Americans will die of the disease and 147,500 new cases will be diagnosed, according to The American Cancer Society.
"Conventional treatments remain relatively ineffective in curing patients with advanced colorectal cancer, so there is a significant need for novel therapies," said the trial's coordinating investigator, Professor Richard H.J. Begent, M.D., head of the oncology department at Royal Free Hospital in London. "The anti-tumor activity exhibited by the combination of (131)I-A5B7 and CA4P in pre-clinical tests suggests that this is a promising therapeutic strategy for patients with this disease."
RIT uses an antibody designed to channel radiation directly to tumors, achieving a targeted therapy. A5B7 belongs to a class of compounds known as "anti-CEA" (carcinoembryonic antigen) antibodies because it targets a glycoprotein known to be present in metastatic colorectal cancer. When it is radiolabeled, A5B7 delivers targeted radiation to the tumor. Professor Begent and his team believe that the infusion of (131)I-A5B7, followed by CA4P, might enhance the effect of the radioimmunotherapy by trapping the antibody in the tumor. The study will include patients with CEA-producing tumors in addition to advanced colorectal carcinoma. Tumor response will be evaluated by a variety of radiological methods.
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CA4P is involved in the following clinical studies:
Trial Combination Indication
Phase II (Single agent) Anaplastic thyroid cancer
Phase I/II (131)I-A5B7 Colorectal cancer
Phase I/II Radiotherapy Lung, head and neck, prostate
cancer
Phase I/II Carboplatin and Ovarian cancer
paclitaxel
Phase Ib(1) Carboplatin Various solid tumors
Phase I/II (Single agent) Wet age-related macular
degeneration
(1) Patient enrollment has concluded. Drug therapy is still being
administered. |
