A Phase I, First-In-Human, Dose-Seeking Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Orally Administered MPT0E028 in Subjects with Advanced Solid Malignancies without Standard Treatment (I)

Histone deacetyIase (HDAC) serves as a potential target for cancer therapy. Vorinostat (Merck & Co.) received marketing approval from the FDA in October, 2006 for the treatment of cutaneous T-cell lymphoma (CTCL). The mechanism acts as an inhibitor for HDAC results in inhibition of tumor cell proliferation and induction of apoptosis. There are many HDAC inhibitors in ongoing clinical trials. The small anticancer molecule, MPT0E028, has been demonstrated as a HDAC inhibitor. The evaluation and validation of anticancer efficacy in 8 mice xenograft model studies, including prostate cancer (PC3), liver cancer (Hep3B), lung cancer (A549), colon cancer (HCT 116), breast cancer (MDA-MB-231), lymphoma (BJAB), leukemia (MOLT-4), and pancreas cancer (AsPC1), showed inhibition of tumor growth but no significant influence on body weight. In addition, oral efficacy of MPT0E028 is better than Vorinostat, Erlotinib, Sorafenib and Gemcitabine; and also showed synergistic effect in combination use with Erlotinib or Sorafenib. We have finished GMP production of API and preclinical studies. Filing IND for FDA and TFDA are on the schedule. This project is an open-label, dose-seeking study evaluating the safety, pharmacokinetics and pharmacodynamics of orally administered MPT0E028 in subjects with advanced solid malignancies based on vital signs, ECG, and laboratory results, etc.