CUDC-101
| About CUDC-101 CUDC-101 is the lead drug candidate from Curis’ multi-targeted cancer programs and is designed to inhibit histone deacetylase (HDAC), epidermal growth factor receptor (EGFR) and epidermal growth factor 2 (Her2). Testing of CUDC-101 was recently completed a Phase I clinical trial in patients with advanced, refractory solid tumors. As Curis’ first multi-targeted inhibitor in clinical development, Curis believes that CUDC-101 is exemplary of the Company’s approach, which aims to enhance the therapeutic effect and durability of clinical response by attacking cancer cells at multiple points of intervention. Curis initiated a Phase Ib expansion trial of CUDC-101 in gastric, head and neck, breast and liver cancers in August 2010, and expects to initiate a Phase I/II clinical trial of the molecule in head and neck cancer patients in the second half of 2010. About the Phase I Clinical Trial Curis concluded the Phase I dose escalation study in March 2010 and determined that 275 milligrams per meter2 represents the maximum tolerated dose, or MTD, of CUDC-101. The Phase I trial was designed as an open-label, dose escalation study of CUDC-101 in patients with advanced, refractory solid tumors. The primary objectives of the Phase I trial were to evaluate the safety and tolerability of escalating doses of CUDC-101 and to establish the MTD and dose limiting toxicities. Secondary objectives were to assess the pharmacokinetics to evaluate pharmacodynamic biomarkers and to assess efficacy and ability of CUDC-101 to inhibit HDAC, EGFR and Her2 in this patient population. The study was conducted at two clinical sites within the United States and enrolled 25 patients across several dose-escalating cohorts. CUDC-101 demonstrated promising evidence of antitumor activity at doses ranging from 150 milligrams per meter2 and 275 milligrams per meter2, including one confirmed partial response that was achieved in a gastric cancer patient at 275 milligrams per meter2, and a stable disease of greater than three months observed in a refractory breast cancer patient cancer patient at 150 milligrams per meter2. Two additional head and neck cancer patients, including one patient with salivary gland adenocarcinoma and one patient with tongue squamous cell carcinoma, exhibited anti-tumor activity with a decrease of greater than 20% in their respective target lesions. CUDC-101 also exhibited what the Company believes to be an acceptable safety profile in the Phase I dose escalation study. The most frequent adverse events were Grade 1-2, or mild to moderate, and included fatigue, vomiting, dyspnea (shortness of breath), pyrexia (fever), and dry skin. Rash was also observed at the 275 milligrams per meter2 dose level. We anticipate that the study’s principal investigator, Dr. Anthony Tolcher of South Texas Accelerated Research Therapeutics (START), will present the Phase I trial data at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held in November 2010 in Berlin, Germany. About the Phase Ib Expansion Trial Curis initiated a Phase Ib expansion trial in August 2010. The study is designed as an open-label study in which a total of approximately 40 patients with advanced, refractory head and neck, gastric, breast and liver cancers are expected to be treated with CUDC-101 at the maximum tolerated dose of 275 milligrams per meter2 at between five and eight study centers in the United States. In subjects with specific advanced solid tumors when the drug is administered either on a five days per week schedule (1 week on/1 week off) or on a three times per week schedule (3 weeks on/1 week off). The secondary study objectives include further evaluation of the pharmacokinetics and pharmacodynamic biomarkers following CUDC-101 administration and to assess the efficacy of CUDC-101 in this patient population. About the Planned Phase I/II Clinical Trial Curis expects to initiate a Phase I/II clinical trial of CUDC-101 in head and neck cancer patients by the end of 2010. While the study design is ongoing, Curis’ management team currently expects that CUDC-101 will be studied in a randomized two-arm trial in which patients will receive cisplatin and radiation plus or minusCUDC-101. The primary objectives of the Phase I portion of this study are to evaluate the safety and tolerability of CUDC-101 when administered in combination with cisplatin and radiation. The Phase II part of the study will seek to evaluate whether the addition of CUDC-101 can improve the efficacy and durability of cisplatin and radiation therapy. Curis selected head and neck cancer as the first indication for potential Phase II testing of CUDC-101 for several reasons. First, CUDC-101 demonstrated biological activity on two patients with head and neck cancer in Phase I dose escalation study, including a mixed response in a head and neck cancer patient at 150 mg/m2 dose level and a tumor reduction of over 20% after just four weeks of study drug administration in another head and neck cancer patient at the 275 mg/m2 dosing level. Second, the Curis research team generated strong in vitro and in vivo preclinical data in head and neck cancer, exemplified by data in seven head and neck cancer cell lines that includes some of the highest potency observed of the cell lines in which CUDC-101 was tested. Lastly, Curis believes that this internal data is supported by published literature demonstrating that both EGFR and Her2 are often implicated in head and neck cancers. |
Retained by Curis |
