NANTES, France, Oct. 3, 2013 (GLOBE NEWSWIRE) -- ATLAB Pharma SAS announces the presentation at the European Cancer Congress 2013 (Amsterdam, Netherlands, Sep 27-Oct 1 2013) of a Phase I with expansion cohorts trial involving 41 patients treated with fractionated doses of ATL101, reporting significant antitumor activity with a trend in dose-dependent effect on overall survival associated to a good tolerance and manageable myelotoxicity.
Dr Scott Tagawa (Weill Cornell Medical College, WCMC, New York) presented the updated results of a dose escalation Phase I trial investigating the safety and the antitumor activity of fractionated radioimmunotherapy with ATL101, followed by an expansion cohort at the Recommended Phase II Doses (RP2D).
41 evaluable patients were treated with two infusions of ATL101 two weeks apart (26 patients at the RP2D and 15 patients at doses below the RP2D). All patients were previously heavily treated (100% with 1-4 hormonal therapies and 40% with 1-4 lines of chemotherapy).
The total dose of 80mCi/m² fractionated in two 40mCi/m² infusions two weeks apart resulted in reversible thrombocytopenia without any clinical complication in 14 patients. In 28% of cases, thrombocytopenia was managed by platelet transfusions. This dose of 80mCi/m² is thus the recommended Phase II dose (RP2D). Another RP2D dose at 90mCi/m2, with the support of blood cell growth factors, was defined in 12 patients. The other significant adverse events were reversible neutropenia, infusion reaction and transaminitis. No complication has been noted.
A decline of blood PSA levels by 50% or more (50% PSA decline) was observed in 27% of patients injected with RP2D vs. 6.7% of patients injected with lower doses. The number of tumor cells counted in the blood also declined 4-6 weeks after treatment in 64% of the 11 patients evaluated for this parameter.
The overall survival was 43.0 months [24.7-63.1] for RP2D patients compared to 15.3 months [4.5-26.0] for patients treated with lower doses.
Dr. Bruno GIROUX, ATLAB's Head of Clinical Development, comments: "This important piece of work concludes that fractionated administration of ATL101 is safer, and probably more efficient, than a single-shot 70mCi/m2 administration, whose Phase II results on 47 patients were published a few weeks ago.
Together with imaging data also published this year, indicating that high ATL101 tumor uptake, as imaged by a gamma camera, may double the response rate and prolong survival, we reached a key milestone in understanding how to use ATL101 to make it a safe drug with a high potential of substantial survival benefit for mCRPC patients.
Our clinical program will now focus on randomized studies aiming at confirming the clinical added value of fractionated ATL101 compared to other therapies and of selecting patients by PSMA imaging and other biomarkers".
Reference
Abstract #2915: Phase I trial of fractionated-dose 177Lutetium radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for metastatic castrate resistant prostate cancer (CRPC). S.T.Tagawa, N.H. Akhtar, A. Nikolopouli, Vallabhajosula, J. Osborne, H Beltran, R.Khan, S.J. Goldsmith, D.M. Nanus, N.H. Bander. Weill Cornell Medical College Medecine, Radiology, Urology New York USA.
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.
About ATL101
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) coupled with Lutetium-177 creating the first tumor-specific delivery system able to target radiation to radio-sensitive prostate cancer cells wherever they are in the body.
ATL101 has shown good tolerance, anti-tumor efficacy and dose response in Phase I and Phase II studies including more than 120 patients with metastatic castrate-resistant prostate cancer (mCRPC).
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 is rapidly internalized leading to accumulation of high radiation dose inside the tumor cell. 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 that is ideal for eradication of 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
A Phase I study (J Clin Oncol 23:4591-4601, 2005) first determined the tolerance and the maximal tolerated dose of a single shot of ATL101 in 35 mCRPC patients at 70mCi/m2.
A Phase 2 study (Clin Cancer Res 19(18):5182-91, 2013) demonstrated anti-tumor efficacy and dose response of a single shot of ATL101 at 65 mCi/m2 and 70mCi/m2 in 47 mCRPC patients.
A Phase I study (NCT00538668, this press release) also determined the tolerance, the maximal tolerated dose, and the antitumor efficacy of fractionated schedules of ATL101 in 41 mCRPC patients.
ATL101 is actively studied at Weill-Cornell Medical College/New York-Presbyterian Hospital in a Phase I trial evaluating combination with docetaxel (NCT00916123) and in a randomized, multicenter Phase II trial in patients who have relapsed following surgery and/or radiation therapy and hormonal therapy but who do not yet have demonstrable metastatic disease (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.
ATL101 _ECC 2013: http://hugin.info/156036/R/1733490/580437.pdf
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