Weill Cornell Researchers: Encouraging Results from J591 Study

Dr. Tagawa
Dr. Tagawa

Weill Cornell researchers recently published findings from a Phase II study of the lutetium-177-labeled monoclonal antibody J591 (called Lu-J591).

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. Scott Tagawa and colleagues at Weill Cornell have been conducting clinical trials of the precision radioimmunotherapeutic J591 to determine its ability to eradicate prostate cancer cells.

In the recently published study, 47 prostate cancer patients with PSA progression after hormonal therapies with or without chemotherapy were treated with Lu-J591. 10.6 percent experienced more than 50% PSA decline, and 36.2% experienced more than 30% decline. Among those treated at the maximum tolerated dose, 46.9% had more than 30% PSA decline. Furthermore, 75% of patients with radiographically measurable disease had some measure of disease control; 67% of those assessed for circulating tumor cells had more than 50% decline in tumor cell counts 4 to 6 weeks after treatment.

The researchers concluded that a single dose of Lu-J591 was well tolerated and they found a measurable response rate. The authors conclude that Lu-J591 is a promising new therapeutic strategy to explore.

Click here to read the published abstract. Click here to read an article about the study and the findings.

Dr. Scott Tagawa Presents Results of PSMA Imaging for Radioimmunotherapy in CRPC at AACR

Dr. Tagawa
Dr. Tagawa

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.