CUDC-101, an experimental drug with a potential to destroy a wide range of cancers including advanced head and neck, gastric, breast and liver cancers, is currently in clinical studies.
Curis, Inc announced that the first patient has been treated in a Phase Ib expansion study for CUDC-101 in patients with advanced head and neck, gastric, breast and liver cancers.
CUDC-101 is a first-in-class small molecule drug candidate that has been designed as an inhibitor of histone deacetylase (HDAC), epidermal growth factor receptor (EGFR) and epidermal growth factor receptor 2 (Her2).
“We are pleased to be participating in this trial with this promising new drug candidate,” commented Dr. John Nemunaitis, M.D., Executive Medical Director at the Mary Crowley Cancer Research Centers, and a principal investigator on the CUDC-101 phase Ib expansion trial.
The preliminary data from the dose escalation phase I study is intriguing, with CUDC-101 having a favorable safety profile and interesting signs of clinical activity being observed, including a partial response in a patient with gastric cancer, he said.
“The Phase Ib expansion trial is designed to target several tumor types that we believe may respond to CUDC-101 based on findings in our Phase I clinical trial and preclinical data, several published reports and clinical outcomes from other drugs that target HDAC, EGFR and Her2,” said Dan Passeri, Curis’ President and Chief Executive Officer.
Curis plans to initiate a Phase I/II clinical trial of CUDC-101 in head and neck cancer patients later this year and are currently working to formalize the design of this study.
The Phase Ib clinical trial expansion 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 meter at between 5 and 8 study centers in the United States.
The primary objectives of this study are to compare the safety and tolerability of CUDC-101 in subjects with specific advanced solid tumors when the drug is administered either on a 5 days per week schedule (1 week on/1 week off) or on a 3 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.
CUDC-101 is designed as a first-in-class therapeutic to simultaneously inhibit HDAC, EGFR and Her2. 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.
Curis-generated 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.
Utilizing the same targeted strategy with other currently available drugs would require combining two or three separate agents, which often have mismatched pharmacokinetic and distribution properties and often display additive dose limiting toxicities.
In contrast, CUDC-101, as a single small molecule, may have the potential to act in the same cancer cells at the same time with fewer toxic side effects and thus potentially represents an important advance in targeted agent cancer therapy.
Curis is a drug development company to create new targeted small molecule drug candidates for cancer.