NANTES, FRANCE--(Marketwire - February 15, 2013) - ATLAB Pharma SAS announces 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) has been presented at the ASCO 2013 Genitourinary cancer meeting (Orlando FL, USA, 14-16 February 2013).
Dr. Scott Tagawa presented the results and survival update of the Phase II clinical trial performed at Weill-Cornell Medical College, New York Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center, aimed at investigating the antitumor activity and safety profile of ATL101.
ATL101 was administered as a single intravenous injection at 2 radioactivity dose levels, 65 or 70 mCi/m², in 2 planned consecutive cohorts (1 and 2) enrolling 15 and 17 mCRPC patients respectively. Subsequently, a third expansion cohort (3) of 15 patients was added at the 70mCi/m² dose. All patients had failed up to 4 hormonal therapies and 55% had also 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.
Assessment of the CTC counts and PSMA antibody imaging are suggested to be useful companion biomarkers.
Pr. Jean-François Chatal, ATLAB's Head of Medical Affairs said: "These results confirm the safety and the antitumor activity of ATL101 in mCRPC. ATL101 shows a steep dose effect on antitumor activity as expected from its radiotherapy mode of action and a potential in prolonging the life of patients with metastatic prostate cancer. This justifies further validation by randomized trials".
Tagawa, ST at al. Phase II trial of 177lutetium radiolabeled anti-PSMA antibody J591 (177Lu-J591) for metastatic castrate-resistant prostate cancer (metCRPC): Survival update and expansion cohort with biomarkers. http://gucasym.asco.org/content/107376-134
About prostate cancer
Prostate cancer is the most common cancer among men with a median survival in metastatic castrate-resistant (mCRPC) disease of 12-24 months.
Prostate cancer is a radiosensitive disease. While localized prostate cancers are commonly treated by radiation, the ability to target radiation to prostate cancer sites elsewhere in the body has been limited until now.
ATL101 is a new targeted radiotherapy drug candidate for treating prostate cancer. ATL101 has shown tolerability profile in a phase I including 35 patients with metastatic castrate-resistant prostate cancer (mCRPC). 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.
Clinical trials with ATL101
ATL101 is actively studied at Weill-Cornell Medical College/New York-Presbyterian Hospital in Phase I trials evaluating fractionated administration (clinicaltrials.gov: NCT00538668) and combination with docetaxel (NCT00916123). 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 (NCT00859781).
About ATLAB Pharma
ATLAB Pharma SAS is a privately-owned biotechnology company headquartered in Nantes, France. ATLAB is developing a pipeline of innovative antibody-based anti-cancer drugs including Lutetium-177 beta-emitting radiopharmaceuticals and Astatine-211 alpha-emitting radiopharmaceuticals.
ATLAB Pharma at ASCO GU 2013: http://hugin.info/156036/R/1678585/547926.pdf