Phase I Study of Efatutazone, an Oral PPARγ Agonist, in Patients with Metastatic Solid Tumors

Background: Efatutazone is a highly selective agonist of peroxisome proliferator-activated receptor gamma (PPAR gamma), a therapeutic target for carcinogenesis. Patients and Methods: In this phase I dose-escalation study, we assessed the safety, efficacy, and pharmacokinetics of efatutazone and the recommended dose (RD) was determined in Japanese patients with metastatic solid tumors using a 3+3 design. Results: A total of 13 patients were enrolled and received efatutazone at doses of 0.25 mg, 0.50 mg, and 0.75 mg bid for multiple 3-week cycles. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. Partial response was confirmed in one patient and stable disease in three. Efatutazone exposure was almost dose-proportional. RD was determined to be 0.50 mg bid, corresponding to the RD in previous global phase I studies. Conclusion: Efatutazone demonstrated acceptable toxicity and gave evidence of disease control in Japanese patients with metastatic solid tumors.