The U.S. Food and Drug Administration (FDA) has cleared Nuvation Bio’s investigational new drug (IND) application to evaluate NUV-868, a BD2-selective oral small molecule bromodomain and extra-terminal (BET) inhibitor, for the treatment of advanced solid tumors, including ovarian cancer, pancreatic cancer, metastatic castration resistant prostate cancer (mCRPC), and triple negative breast cancer (TNBC).
“The clearance of our IND application for NUV-868 is an important milestone for Nuvation Bio as it marks the fourth IND in the last 14 months across our deep pipeline of innovative cancer therapeutics targeting multiple tumor types,” said David Hung, M.D., founder, president, and Chief Executive Officer of Nuvation Bio.
“We are encouraged by the selectivity and potentially improved tolerability demonstrated by NUV-868 in preclinical studies, and we look forward to advancing the program into Phase 1 development in mid-2022.”
NUV-868 inhibits BRD4, which is a key member of the BET family that epigenetically regulates proteins that control tumor growth and differentiation. NUV-868 is designed to be more selective for BD2 than BD1 in an attempt to avoid the therapeutic limiting toxicities of other BRD4 inhibitors like gastrointestinal (GI) and bone marrow toxicities. Preclinical studies have demonstrated NUV-868 is almost 1,500 times more selective for BD2 than BD1. Non-selective BD1/2 inhibitors in development have been associated with tolerability issues, potentially due to too much BD1 inhibition.
With the clearance of this IND for NUV-868 in advanced solid tumors, Nuvation Bio will be initiating a Phase 1/2 study of NUV-868 as a monotherapy and in combination with olaparib or enzalutamide in multiple tumor types. This protocol (NUV-868-01) will begin with a Phase 1 monotherapy dose escalation study in advanced solid tumor patients.
A Phase 1b study will then be initiated exploring NUV-868 in combination with olaparib in previously treated ovarian cancer, pancreatic cancer, mCRPC, and TNBC patients and in combination with enzalutamide for mCRPC patients followed by a Phase 2b study to further explore safety and efficacy once the recommended Phase 2 combination dose is determined. A Phase 2 monotherapy study will also be initiated in mCRPC patients as well to further explore safety and efficacy.
