Ariad posted some phase I results for deforolimus that look encouraging for soft-tissue sarcoma generally:
Abstract No:
3509
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 3509)
Author(s):
M. M. Mita, C. D. Britten, E. Poplin, W. D. Tap, A. Carmona, L. Yonemoto, D. S. Wages, C. L. Bedrosian, E. H. Rubin, A. W. Tolcher
Abstract:
Background: Deforolimus is a non-pro-drug rapamycin analog which specifically and potently inhibits mTOR. In Trial 202 intravenous deforolimus demonstrated notable anti-tumor activity in bone and soft tissue sarcomas. (JCO 2006; 24, 18S: 9505). Oral deforolimus allows greater treatment flexibility and offers potential to treat patients in a maintenance setting. We report preliminary results on oral deforolimus in a comprehensive dose finding study in patients (pts) with refractory malignancies. Methods: The trial was an open label single arm study with dose escalation and a standard 3+3 design. Patients had advanced/metastatic solid tumors refractory to therapy. 7 regimens, all over a 28 day cycle were investigated. Definitions of dose limiting toxicity (DLT; Gr 4 or Gr 3>3 days) were based on CTC criteria. Anti-tumor activity was evaluated by modified RECIST criteria. Patients achieving stable disease (SD) or better lasting for at least 4 cycles of 28 days were classified as achieving clinical benefit response (CBR). Results: 147 pts (85 sarcoma) received deforolimus. Median age was 56 (range 23-84 years); 65 (44%) pts were male. Pts had a median of 2 cytotoxic therapies at entry (range 0-7); 113 (77%) of this population had documented progressing disease at enrollment. The median ECOG score was 1 (range 0-2). The DLT for all regimens was aphthous-ulcer like mouth sores which were reversible by dose reduction or symptomatic therapy. 36 pts achieved CBRs (23 sarcomas). MTD was increased with the addition of a weekly dose holiday interval. CBRs were seen in all regimens and several types of sarcomas and a variety of carcinomas. 24 pts received 40 mg QDx5/wk and in this group 3 of 13 (23%) sarcomas had CBR; 2 (liposarcoma, dendritic cell sarcoma) (15.4%) achieved PR. Pharmacodynamic analysis showed potent inhibition of mTOR. 7 patients remain on therapy after 6-24 cycles. Conclusions: Oral deforolimus has a safety and anti-tumor activity profile consistent with the intravenous form. 40 mg QDx5 each week is an active, well tolerated regimen and has been selected for further evaluation in SUCCEED, a global phase 3 trial of patients with metastatic soft-tissue and bone sarcoma in the maintenance setting.
No comments:
Post a Comment