Date: 2013-10-03
Type of information:
phase: 1
Announcement: presentation of results at the European Cancer Congress ECC 2013.
Company: Atlab Pharma (France)
Product: ATL101 (Lutetium-177 anti-PSMA antibody)
Action
mechanism: 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. 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.
Disease: metastatic castrate-resistant prostate cancer (mCRPC)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase 2 Trial of 177Lu radiolabeled monoclonal antibody HuJ591-GS (177Lu-J591) in patients with metastatic androgen-independent prostate cancer has been performed by the Weill-Cornell Medical College. The purpose of the study is to find out how effective 177Lu -J591 is in the treatment of patients with metastatic, androgen-independent prostate cancer.
Patients have received a single dose of J591 (total antibody of 20 mg) consisting of antibody chelated with 177Lu at a dose of 65 or 70 mCi/m2 with a specific activity of 12-15 mCi/mg plus non-radiolabeled antibody. (NCT00195039)
Latest
news: * On October 3, 2013, ATLAB Pharma has announced the presentation at the European Cancer Congress 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. (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).
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).
* On February 15, 2013, ATLAB Pharma hase 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) 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. 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.
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.
