Dr. Tagawa Presents Updated Results of ATL101 at AACR

At the annual American Association for Cancer Research in Washington, DC last week, Dr. Scott Tagawa presented updated combined analysis of 4 Phase I and Phase II studies involving 114 patients treated with ATL101. The analysis demonstrated that PSMA imaging might be used to predict the response to ATL101 radioimmunotherapy.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.

From the sponsor’s press release:

14 patients were evaluable for semi-quantitative analysis of planar gamma images acquired after injection of ATL101 (35 patients from phase I at dose of 10-75 mCi/m²; 47 patients from Phase II at dose of 65-70 mCi/m² and 39 patients from phase I with a fractionated schedule at dose of 40-90 mCi/m²). 22 patients were also evaluable after injection of Indium-111 labeled J591 and treatment by Yttrium-90 labeled J591 at dose of 5-20mCi/m². Patients were sorted into 3 groups: low PSMA expression group included one third of patients, with no uptake (18%) or with weakly positive images (16%); high PSMA expression group included one half of patients, with tumor image as intense (26%) or more intense (24%) than liver. The 16 % remaining patients had intermediate uptake.

Significant correlation was found between higher PSMA expression (high vs. low) and higher response rates (RR) to treatment defined as >30% decline in PSA (RR=32% vs. 12.5%, p=0.01). RR was itself significantly correlated to longer survival. An association between PSMA expression by imaging and reduction in circulating tumor cell counts was also found (p=0.07). Further studies will examine quantitative molecular imaging with anti-PSMA PET/CT as recently published in animal models (Morris et al, 2013 ASCO Genitourinary Cancers Symposium).

Click here to read the complete press release.

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.

Weill Cornell’s Dr. Scott Tagawa Presents Positive Results of ATL101 at ASCO

ATLAB Pharma SAS announced that positive results of a phase II study of ATL101 (Lutetium-177 anti-PSMA antibody) on 47 patients with progressive metastatic castrate-resistant prostate cancer (mCRPC) have been presented at the ASCO 2013 Genitourinary cancer meeting.

Weill Cornell’s Dr. Scott Tagawa presented the results and the survival update. The study was performed at Weill Cornell Medical College/NewYork-Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center.

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.

In the study, ATL101 was administered as a single intravenous injection at 2 radioactivity dose levels, 65 or 70 mCi/m^2, in two consecutive cohorts of patients with metastatic castration-resistant prostate cancer (mCRPC). A third cohort was added at the 70mCi/m^2 dose. All patients had failed up to 4 hormonal therapies, and 55% of the patients had failed at least one docetaxel-containing chemotherapy regimen.

The results suggested a statistically significant relationship between injected dose and antitumor activity. The percentage of patients achieving PSA decline over 30% (30% PSA decline) increased from 13 % in Cohort (1) to 47 % in Cohort (2). The expansion Cohort 3 confirmed the rates of 30% PSA decline at 47% of patients. A treatment effect on the circulating tumor cells (CTC) count was also observed. Moreover, median overall survival (OS) significantly increased with the injected dose of radioactivity from 11.9 months in cohort (1) to 21.8 months in cohorts 2 and 3. The treatment was well tolerated with predictable, transient, and manageable dose-related changes in blood cell counts. Patients experienced no serious symptomatic side effects.

ATL101 is actively studied at Weill-Cornell Medical College/New York-Presbyterian Hospital in Phase I trials evaluating fractionated administration and combination 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 view the Phase II trial at clinicaltrials.gov.