[Interim PII results for AP23573 in sarcoma]
>>PHILADELPHIA and CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 16, 2005--ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA - News) today announced interim results of an ongoing Phase 2 clinical trial of its novel mTOR inhibitor, AP23573, administered as a single agent, in patients with advanced bone and soft-tissue sarcomas. Twenty-seven percent (27%) of 188 evaluable patients treated with AP23573 had sustained tumor regression and/or disease stabilization. In addition, the six-month progression-free survival (PFS) rate in AP23573-treated patients in the first stage of the trial was 22%, which compares favorably to historical data on soft-tissue sarcoma patients treated with inactive chemotherapies for whom the six-month PFS was estimated to be only 8% (van Glabbeke et al, 2002). Almost all patients in the current trial had failed alternative anti-cancer treatments and had progressive disease upon entering the trial.
"These results provide compelling evidence of the potential clinical utility of AP23573 in patients with advanced sarcomas - a cancer with limited treatment options available. AP23573 was chosen by the AACR-NCI-EORTC (ANE) to be highlighted as one of the exciting new drugs in development in its news briefing this morning and as an oral proffered paper in the scientific program tomorrow afternoon," said Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD.
"In clinical trials to date, AP23573 treatment has produced a high level of durable disease stabilization and symptomatic improvement in patients with advanced sarcomas," said Sant P. Chawla, M.D., one of the lead investigators in the AP23573 Sarcoma Study Group, who presented top-line findings from the study at the ANE press briefing this morning. "As we continue to study AP23573 in sarcomas, I am excited about the potential AP23573 may offer in the fight against this devastating cancer."
Trial Objectives and Design
The primary objective of this multi-center clinical trial is to assess the efficacy and safety of AP23573 in four groups of advanced sarcomas: (a) bone sarcomas (b) leiomyosarcoma, (c) liposarcoma, and (d) other soft-tissue sarcomas. The trial began patient enrollment about one year ago in October 2004. Patients receive a fixed dose of 12.5 mg of AP23573 intravenously using a daily dosing regimen of drug (i.e., five days on, nine days off, drug).
The trial uses Simon's two-stage design within each of these sarcoma groups. Four of the initial 19 patients within each group (stage 1) must exhibit a predefined four-month clinical-benefit response based on strict Response Evaluation Criteria in Solid Tumors (RECIST) guidelines before the group can be expanded and enrollment to at least 44 patients continued. While the patients enrolled in each cohort in stage 1 of the trial were being followed, further enrollment into the groups was paused even as additional patients were being identified for possible enrollment into the second stage. The strict criteria for continued enrollment were met in all four groups, and subsequently patients were enrolled in stage 2 of each group. Enrollment in the trial has exceeded projected targets due to high patient and clinician interest in AP23573. The trial was designed to determine whether a clinical-benefit response rate of at least 25% was achieved in each sarcoma group.
A total of 212 patients were enrolled to date: 82 in stage 1 and 130 in stage 2. Four of these patients were not dosed, and six additional liposarcoma patients have been screened and may be enrolled. Recruitment of patients for the trial is complete. As of the date of analysis, 81 of the stage 1 patients and 107 of stage 2 patients were evaluable through at least four months on AP23573 treatment - the minimum duration for assessing protocol-defined clinical-benefit response. Patients continue on AP23573 until their disease progresses.
Six-month progression-free survival (PFS), a key endpoint for evaluating the efficacy of AP23573, was determined using the Kaplan-Meier analysis of the stage 1 patients and will be determined in the entire study population once all patients have been followed further.
Results of Interim Analysis
AP23573 treatment achieved the predefined threshold for efficacy (i.e., at least 25% clinical-benefit response rate) in the bone sarcoma group (29%) and the most common of the soft-tissue sarcoma groups - leiomyosarcoma (36%). The results in the liposarcoma group (17%) are too early to evaluate, as patients have not been followed long enough, and the results in the other soft-tissue sarcoma group, a heterogeneous group of multiple different types of soft-tissue sarcomas, are close to meeting this threshold (22%). The overall clinical-benefit response rate for the entire trial is 27%.
Thirty-three percent (33%) of the stage 1 patients (27/81) in the trial have clinical-benefit responses - sustained anti-tumor activity - including four patients with partial responses (confirmed tumor regression greater than 30%) and 23 patients with stable disease for at least four months. Clinical-benefit responses were demonstrated in 39% of bone sarcoma patients, 50% of leiomyosarcoma, 21% of liposarcoma, and 24% of other soft-tissue sarcomas. The six-month PFS rate in this group is 22%.
Twenty-two percent (22%) of the evaluable stage 2 patients (24/107) in the trial have clinical-benefit responses - sustained anti-tumor activity - at this time. The comparability of the patient populations in the two stages of the trial is being evaluated further. Assessment of PFS for the entire trial awaits follow up of the stage 2 patients as the data mature.
AP23573 was well tolerated at the fixed dose administered, and adverse events were generally mild to moderate in severity and readily reversible. The most common treatment-related adverse events were oral mucositis, rash, fatigue, nausea and hyper-triglyceridemia.
"These data provide valuable insights into the efficacy and safety profile of AP23573 in sarcoma patients and further refine our understanding of those patients likely to benefit most from AP23573. The results to date have guided our design considerations for the initial registration trial for AP23573," said Camille L. Bedrosian, M.D., chief medical officer of ARIAD. "Progression-free survival is a valuable endpoint in this patient population and may be a strong predictor of survival benefit. Clearly these data support further study of AP23573 in a randomized pivotal trial of patients with advanced sarcomas."
These clinical results are being presented by Sant P. Chawla, M.D. on behalf of the AP23573 Sarcoma Study Group as oral presentations at the 17th ANE International Conference on "Molecular Targets and Cancer Therapeutics" in Philadelphia, Pennsylvania, November 17, 2005 and the 11th Annual Connective Tissue Oncology Society (CTOS) Meeting in Boca Raton, Florida, November 20, 2005. More information about the ANE conference and the news briefings can be found on the web at aacr.org. <<
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Cheers, Tuck |
