Ariad Pharmaceuticals reports that ridaforolimus met the primary endpoint of improved progression-free survival (PFS) compared to placebo in the Phase III SUCCEED trial conducted in patients with metastatic soft-tissue or bone sarcomas who previously had a favorable response to chemotherapy. Merck & Co. is currently developing this oral mTOR inhibitor in multiple cancer indications under an exclusive license and collaboration agreement with Ariad.
Based on the full analysis of 552 PFS events in 711 patients, determined by an independent review committee, the blinded prospective study achieved its primary endpoint, with a statistically significant 28% reduction by ridaforolimus in the risk of progression compared to placebo. Determination of median PFS for each arm of the trial demonstrated that ridaforolimus treatment resulted in a statistically significant 21% (3.1 week) improvement in median PFS (ridaforolimus, 17.7 weeks vs. placebo, 14.6 weeks).
This trial remains active, and study participants continue to be followed to gather additional data on secondary endpoints including overall survival and the safety profile of ridaforolimus. Merck plans to file for marketing approval this year.
The SUCCEED trial is a randomized, placebo-controlled, double-blind study of oral ridaforolimus administered at 40 mg/day (five of seven days/week). mTOR acts as a central regulator of protein synthesis, cell proliferation, cell-cycle progression, and cell survival. It integrates signals from proteins such as PI3K, AKT and PTEN, which are known to be important to malignancy.