About the Phase I Combination Trial
The Phase I clinical trial is designed as an open-label, dose escalation study in which a total of approximately 15-25 human papillomavirus negative (HPV-) locally advanced head and neck cancer patients will be treated with CUDC-101 in combination with cisplatin and radiation at four study centers in the United States. The primary objective of this study is to establish the safety, tolerability and maximum tolerated dose (MTD) of CUDC-101 in this patient population. Secondary objectives are to (i) evaluate the efficacy of CUDC-101, cisplatin and radiation therapy combination, (ii) assess the pharmacokinetics of CUDC-101, and (iii) evaluate tumor markers for response associated with CUDC-101, cisplatin and radiation activity. CUDC-101 will be administered three times per week for 8 consecutive weeks, with a beginning dose of 225 milligrams per meter 2. The MTD of CUDC-101 in a previously completed single agent Phase I clinical trial was established as 275 milligrams per meter 2.
Upon determination of the MTD and assuming the otherwise successful completion of this Phase I combination trial, Curis plans to conduct a randomized Phase II two-arm clinical trial in which head and neck cancer patients will receive cisplatin and radiation plus or minus CUDC-101. It is currently expected that the Phase II study would seek to evaluate whether the addition of CUDC-101 can improve the efficacy and/or durability of cisplatin and radiation therapy in this patient population.
About CUDC-101CUDC-101 is designed as a first-in-class therapeutic to simultaneously inhibit EGFR, Her2 and HDAC. In preclinical studies, CUDC-101 demonstrated the potential to inhibit all three molecular targets resulting in the potent killing of a wide range of cancer cell lines that are representative of a variety of human cancer types, many of which have demonstrated resistance to various approved targeted agents.