Interim results of a phase I trial with a novel orally administered synthetic triterpenoid RTA 402 (CDDO-Me) in patients with solid tumors and lymphoid malignancies

14101 Background: RTA 402 (CDDO-Me) is a novel synthetic triterpenoid with potent anticancer and anti-inflammatory activity through selective modulation of proteins that respond to changes in oxidative stress, including NF-κB, JNK, and STAT3. Based on preclinical data demonstrating effects on tumors and associated stroma, a Phase 1 dose-finding and pharmacokinetic study was initiated. Methods: RTA 402 is administered orally once a day for the first 21 days of a 28-day cycle. Dose escalation is proceeding according to an accelerated titration design until an MTD is reached. Results: RTA 402 has been administered to 11 patients at 7 dose levels (5 to 300 mg/day). Cycle 1 data are available for 8 patients. No significant drug-related toxicity has been reported and dose escalation continues in 100% increments. The median biological half-life of RTA 402 was 49 h (range, 18–67 h), and all patients receiving doses >20 mg/day were continuously exposed to plasma levels of the drug exceeding 1 ng/mL. Evidence of an...