NANTES, FRANCE--(Marketwired - April 11, 2013) - ATLAB Pharma SAS announces the presentation at AACR 2013 (Washington DC, USA, April 6-10, 2013) of an updated combined analysis of 4 Phase I and Phase II studies involving 114 patients treated with ATL101 demonstrating that PSMA imaging might be used to predict response to ATL101 radioimmunotherapy.
Dr Scott Tagawa presented the updated results of PSMA imaging in 4 therapeutic phase I and II clinical trials performed at Weill-Cornell Medical College, New York Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center, investigating the antitumor activity and safety profile of ATL101 (Lutetium-177 labeled J591 anti-PSMA antibody) and Yttrium-90 labeled J591.
114 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).
Pr. Jean-François Chatal, ATLAB's Head of Medical Affairs, comments: "This preliminary study documents the potential interest in precision medicine and selecting patients for ATL101 radioimmunotherapy on the basis of pre-therapeutic PSMA imaging. However, as only 18% of patients have negative 2D image, the economic and clinical utility of such companion diagnostics should be prospectively validated in further clinical studies using more sensitive and quantitative PET/CT PSMA 3D imaging".
Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy. (Poster #4696). Naveed H. Akhtar, Joseph Osborne, David M. Nanus, Shankar Vallabhajosula, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa
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 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 beta radiation over a millimeter range that is ideal for eradication of the small volume lesions commonly found in the bone marrow and lymph nodes of prostate cancer patients. It also emits gamma ray that can be used for planar scintigraphic imaging.
Clinical trials with ATL101
ATL101 has shown good tolerance, anti-tumor efficacy and dose response in Phase I and Phase II studies including 82 patients with metastatic castrate-resistant prostate cancer (mCRPC).
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-center 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 - AACR 2013: http://hugin.info/156036/R/1692304/555927.pdf