Researchers at NewYork-Presbyterian/Weill Cornell Report Findings of Phase I Clinical Trial of Monoclonal Antibody Treatment for Advanced Prostate Cancer

Investigational Compound J591 Demonstrates Evidence of Anti-Tumor Activity Multi-Center Phase II Clinical Trial Expected to Begin Later This Year

Jul 7, 2004

New York, NY

Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have released final findings of a Phase I trial of an investigational drug, radiolabeled J591, in patients with advanced prostate cancer. J591 is a de-immunized monoclonal antibody therapeutic that was developed at Weill Cornell Medical College. In this trial, published in the July 1 issue of Journal of Clinical Oncology, the antibody delivered radiation directly to prostate cancer sites. The treatment was well tolerated and demonstrated anti-tumor activity.

As a result of these promising findings, a Phase II protocol designed to evaluate anti-tumor activity of radiolabeled J591 has been accepted by the Food and Drug Administration and is expected to begin patient entry later this year. This multi-center trial will be led by NewYork-Presbyterian/Weill Cornell along with NewYork-Presbyterian/Columbia and Memorial Sloan-Kettering Cancer Center.

J591 works by targeting a molecule called prostate specific membrane antigen (PSMA), a protein located on the surface of all prostate cancer cells. PSMA expression is minimal in normal prostate tissue and is greatly increased in prostate cancer. In this trial, J591 was labeled with or carried a radioactive isotope. The goal of this targeted therapeutic approach is to use J591 to selectively deliver radiation to the tumor cells, thereby minimizing exposure of radiation to normal cells.

Prostate cancer is the third most common cause of cancer deaths in men. Once cancer cells escape the prostate, the current standard of care is hormonal treatment. Hormonal therapy causes side effects including hot flashes, sweats, weight gain, muscle wasting, thinning of the bone, fatigue, weakness, and anemia. Furthermore, hormonal therapy is palliative and not curative; all patients ultimately become refractory to its effects.

Early results with J591 suggest that it is a promising new approach that could fill a substantial, unmet medical need, said lead study investigator Neil H. Bander, M.D., the Bernard and Josephine Chaus Professor of Urologic Oncology at Weill Cornell Medical College, and Director of Urologic Oncology and Attending Urologist at NewYork-Presbyterian/Weill Cornell. We are encouraged to continue studies to assess the optimal dose, schedule, and duration of therapy so that the role of this targeted compound in the treatment of prostate cancer can be determined.

Study Findings

The published clinical trial evaluated the effects of the radioisotope 90Y (Yttrium) attached to J591. The study included 29 patients whose prostate cancer had spread throughout the body and whose disease was progressing despite both hormonal treatment and, in almost 40% of cases, chemotherapy. In this Phase I study, the dose of isotope attached to J591 was progressively increased in groups of patients in order to determine the maximum tolerated dose. The radiolabeled antibody was found to be well tolerated by the patients; blood tests revealed an expected drop in platelet and white blood cell counts that spontaneously returned to or near normal. The maximum tolerated dose of the radiolabeled antibody was determined in this clinical trial.

Although this was a Phase I trial, designed primarily to define dose and toxicity rather than anti-tumor response, J591 demonstrated anti-tumor activity. Radiolabeled J591 reduced prostate specific antigen (PSA) levels by as much as 85% and measurable tumor lesions by 90% for periods of up to and beyond eight months. PSA is a protein produced by prostate cells that can be detected in the blood. In prostate cancer patients, changes in PSA levels generally reflect whether a prostate cancer is worsening or improving. Several previous clinical trial publications have indicated that treatment-related PSA declines of greater than 50% correlate with improved survival.

In addition to Dr. Bander, collaborating authors on the study included Drs. Matthew I. Milowsky (first author), David M. Nanus, Lale Kostakoglu, Shankar Vallabhajosula, and Stanley J. Goldsmith all of NewYork-Presbyterian/Weill Cornell.

The study was funded by the NIH General Clinical Research Center Program; the Cancer Research Institute; the David H. Koch Foundation; the Peter Sacerdote Foundation; the Robert H. McCooey Memorial Cancer Research Fund; BZL Biologics, Inc.; and Millennium Pharmaceuticals, Inc.

About Prostate Cancer

According to the National Cancer Institute, there are approximately 1.7 million men living in the U.S. with a diagnosis of prostate cancer. To this number, approximately 230,000 new cases of prostate cancer will be diagnosed, and 29,900 men will die of the disease this year in the United States. The five-year survival rate of men with prostate cancer is 89%, with this percentage jumping to 100% if the cancer is found before it metastasizes (spreads to another area of the body). Today, there is a tremendous, unmet medical need for treating the disease, particularly for end-stage or hormone-refractory prostate cancer. Early detection is important, and the American Cancer Society recommends that men over the age of 50 have a PSA blood test every year. Coupled with a digital rectal exam (DRE), the PSA is a very useful test for determining which men need further evaluation.

About J591 Development Plans

The monoclonal antibody J591 was developed in the laboratory of Dr. Neil Bander at Weill Cornell Medical College and licensed to BZL Biologics, Inc. Dr. Bander serves as a consultant to BZL Biologics, Inc. In April 2001, Millennium Pharmaceuticals, Inc. (NASDAQ: MLNM) entered into an agreement with BZL Biologics, L.L.C., for the joint development and commercialization of antibody-based therapeutics targeting PSMA, including both chemotherapeutic agent conjugated and radio-labeled products. These products include MLN2704 and J591RL. Millennium currently has exclusive development and worldwide marketing rights to these products.

About NewYork-Presbyterian Hospital/Weill Cornell Medical Center

The NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching Hospital NewYork-Presbyterian and its academic partner Weill Cornell Medical College. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory, and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education, and community service. Along with Weill Cornell, Columbia University College of Physicians Surgeons is NewYork-Presbyterian's major academic affiliate.