Curis data suggest that CUDC-101’s mechanism of action involves the sensitization of cancer cells to EGFR and Her2 inhibition through HDAC inhibition. CUDC-101 is designed to simultaneously inhibit both EGFR and Her2 at the receptor level while inhibiting downstream HDAC activity within the cancer cells. Despite the existence of other multi-targeted inhibitors, CUDC-101 is unique in its choice of targets, which may enable a synergistic attack on multiple nodes or points in the overall cancer pathway network that are used by tumors to survive, grow, and invade surrounding tissue.
Curis has completed a Phase I dose escalation clinical trial of CUDC-101 in 25 patients with advanced, refractory solid tumors and has also enrolled 45 of 50 patients in an ongoing Phase I expansion trial to test CUDC-101 in patients with specific tumor types, including breast, gastric, head and neck, liver and non-small cell lung cancers. The Phase I expansion trial is designed as an open-label study in which patients are treated with CUDC-101 at the MTD of 275 milligrams per meter 2. The primary objectives of this study are to compare the safety and tolerability of CUDC-101 in subjects with these specific advanced solid tumors when the drug is administered either on a five days per week schedule (one week on/one week off) or on a three days per week schedule (three weeks on/one week off).
The safety profile observed to-date for both dosing schedules appears to be generally consistent with that observed in the Phase I dose escalation study, in which the most frequent adverse events observed were mild to moderate and included fatigue, vomiting, dyspnea (shortness of breath), pyrexia (fever), and dry skin. In addition, stable disease was observed in several patients in this study. Most notably, stable disease was observed in four patients with advanced liver cancer. Two of these patients have been treated with CUDC-101 for over six months, with one patient remaining on study after 11 months. We have also observed ongoing stable disease of greater than 10 months in an advanced breast cancer patient.