Weill Cornell’s Dr. Scott Tagawa presented four research posters at this year’s American Association for Cancer Research (AACR) annual meeting. Each of the presentations is summarized below. Click on the title to view the published abstracts.
J591 is a man-made monoclonal antibody that is able to recognize a protein antigen (PSMA) expressed on virtually all prostate cancer cells, and more so in men with treatment-resistant metastatic disease. When a tiny tag of radioactive material is attached to the J591 antibody, that specifically targets prostate cancer cells, and delivered systemically this is known as radioimmunotherapy. Dr. Tagawa has been conducting clinical trials of the precision radioimmunotherapeutic J591 to determine its ability to eradicate prostate cancer cells that have metastasized. In this poster presentation, Tagawa and colleagues performed a combined analysis of four clinical studies of this radioimmunotherapeutic that examined 130 patients with metastatic treatment-resistant prostate cancer. They found that the levels of PSMA expression—as determined by a non-invasive scan–can be used to indicate response to their radioimmunotherapy.
Taxanes are a type of chemotherapy drug that are used to treat advanced prostate cancer; however, inevitably prostate cancer patients develop resistance to these chemotherapy drugs. In this poster, Tagawa et al demonstrate that a genetic abnormality (ERG positivity) found in half of all men with prostate cancer plays an active role in inducing resistance to taxane-based chemotherapeutics. Additionally they’ve determined that men with ERG positive tumors have upregulation of another protein (clusterin) that can cause resistance to taxane chemotherapeutics. This work dovetails nicely with Dr. Zoubeidi’s work (see above) and shows the potential to use a drug now in clinical trials (OGX-011) to enhance response to chemotherapy in men whose prostate cancer is positive for the ERG genetic aberration.
This poster describes a prospective, randomized multi-site clinical trial that will enroll 100 men with treatment resistant prostate cancer and use advanced technology to capture and analyze cancer cells that are freely circulating in their bloodstreams. This trial will allow the researchers to look for early signs of treatment response or failure in individual cancer cells and examine the genetic and other molecular factors that indicate or lead to either a response or lack of response to chemotherapy. This is one of the few studies to utilize blood-based biomarkers in a prospective fashion. It is also a demonstration of cooperation between academic partners and the pharmaceutical industry—one that was facilitated by the Prostate Cancer Foundation.
This poster describes a molecular dance that prostate tumor cells exploit as they metastasize to bone. Understanding and characterizing the mechanisms that tumor cells use exit the bloodstream and to home to bone and set up shop should allow researchers to develop ways to interrupt the process and prevent circulating prostate cancer tumor cells from setting up cancerous shop in men’s bones.
Weill Cornell’s Dr. Scott Tagawa presented updated results of PSMA imaging in 4 phase I and II clinical trials at the recent annual meeting of the American Association of for Cancer Research (AACR) in Washington, DC. The trials presented were performed at Weill-Cornell Medical College, New York Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center. The trials investigated the antitumor activity and safety profile of the experimental drug ATL101. The 4 trials involved patients treated with ATL101 and demonstrated that PSMA imaging might be used to predict response to ATL101 radioimmunotherapy in metastatic castrate-resistant prostate cancer patients.
ATL101 is a new targeted radiotherapy experimental drug for treating prostate cancer. ATL101 combines the humanized J591 monoclonal antibody targeting prostate-specific membrane antigen (PSMA) plus the Lutetium-177 radioisotope, creating the first tumor-specific delivery system able to target radiation to radio-sensitive prostate cancer cells wherever they are in the body.
PSMA is the single most well-validated prostate cancer-specific cell membrane antigen known. It is present at high levels in 95% of prostate cancers, and it is rapidly internalized leading to accumulation of significant amounts of isotopes that can be linked to the J591 antibody. Humanized J591 monoclonal antibody has shown the ability, in several hundred patients studied to date, to exclusively target prostate cancer cells wherever they are in the body without targeting normal cells.
Lutetium-177 is a radioisotope that, once internalized into the cell, is irreversibly sequestered within the targeted tumor cell. It emits radiation over a millimetre range that is ideal for eradication of the small volume lesions commonly found in the bone marrow and lymph nodes of prostate cancer patients.
ATL101 is actively studied at Weill-Cornell Medical College/New York-Presbyterian Hospital in Phase I trials evaluating fractionated administration andcombination with docetaxel. In addition, a randomized, multi-centre Phase II trial of ATL-101 in patients who have relapsed following surgery and/or radiation therapy and hormonal therapy but who do not yet have demonstrable metastatic disease is ongoing at several clinical sites in the USA.
Click here to read a press release summarizing the updated results presented by Dr. Tagawa.
The Weill Cornell Urological Oncology Program has recently opened a new clinical trial for for men with metastatic castrate resistant prostate cancer (CRPC) whose cancer has gotten worse after other treatments. The study is evaluating an experimental drug called cabozantinib (XL184). The sponsor of the study is Exelixis, and the principal investigator at Weill Cornell is Dr. Himisha Beltran.
For more information about the study, please call Renee Khan, RN at (212) 746-1851, e-mail Renee at firstname.lastname@example.org.
Metastatic castration-resistant prostate cancer
Evidence of bone metastasis related to prostate cancer
Must have received prior treatment with docetaxel and either abiraterone or MDV3100 and have had disease progression on each medication
Detailed eligibility reviewed when you contact the study team
The purpose of the study is to determine if cabozantinib is effective in prolonging survival compared to the drug prednisone. The study will also evaluate the safety of cabozantinib and how well people with advanced prostate cancer tolerate the drug. In an ongoing study, cabozantinib treatment has resulted in high rates of pain relief and has shown substantial anti-tumor activity. Cabozantinib could provide a valuable new treatment option for men with CRPC who experience disease progression on or after prior therapies.
Study participants will be randomly assigned to one of two treatment groups:
Group 1: cabozantinib once daily + placebo prednisone twice daily
Group 2: Prednisone twice daily + placebo cabozantinib once daily
Participants have a 2/3 chance of receiving cabozantinib (Group 1) and a 1/3 chance of receiving prednisone (Group 2). Participants will not know which treatment they are receiving. Cabozantinib is a capsule and prednisone is a tablet, both taken by mouth.
Participants will continue to receive study treatment as long as they continue to receive clinical benefit and do not experience unacceptable side effects.
Click here to view all current prostate cancer clinical trials in the Department of Medicine.