In the absence of dose limiting toxicity, each patient will receive oral CUDC-907 once daily for a minimum of 21 days of continuous daily dosing (1 cycle), and may continue to receive additional cycles of study treatment until disease progression or other treatment discontinuation criteria are met. Additional details about this study can be found on clinicaltrials.gov (NCT01742988).
CUDC-907 is a dual inhibitor of the Class I PI3K and Class I and II HDAC subtypes, the combination of which Curis scientists believe has synergistic interaction against cancer cells and their microenvironment. In preclinical studies, CUDC-907 has demonstrated the ability to suppress multiple nodes of survival and proliferation. In addition, preclinical data have shown that CUDC-907 inhibits compensatory pathways often utilized in cancer cells during the emergence of resistance to standard of care agents and induces apoptosis in treated cancer cells.
CUDC-907 exhibits anti-proliferation activity against a broad range of cancer cell types in in vitro studies, including cell lines that exhibit reduced sensitivity to single-target PI3K inhibitors. CUDC-907's anti-proliferation activity has been demonstrated to be much more potent than that of leading PI3K inhibitors in development. CUDC-907 also inhibits tumor growth in preclinical xenograft models of blood cancers as well as solid tumors with K-RAS mutations that exhibit reduced sensitivity to known PI3K inhibitors, indicating that this compound may have the potential for broader activity than other leading PI3K inhibitors currently in clinical development.About the LLS Agreement Under the agreement between Curis and LLS, LLS has agreed to fund approximately 50% of the direct costs of the development of CUDC-907, up to $4 million, of which Curis received $1.1 million in funding to date. As noted above, Curis has initiated a Phase I dose escalation clinical trial in patients with relapsed or refractory lymphomas or multiple myeloma. Provided that the Phase I study is successful, the agreement also provides for LLS to support Curis' subsequent Phase Ib or Phase IIa study in one or more specific indications as well as Curis' ongoing investigation of biomarkers for CUDC-907 in these diseases.