"We are profoundly grateful to and inspired by this patient and all other patients who volunteer to participate in clinical trials. Our thoughts are with this patient's family and loved ones," said Ali Fattaey, President and Chief Operating Officer of Curis.
Dr. Fattaey continued, "Based on available data from treated patients, we believe that CUDC-427 could play an important role in oncology treatment, either as monotherapy or in combination with other anticancer agents. Accordingly, we will work diligently to address the FDA's request in an effort to resolve the partial clinical hold."
Curis licensed CUDC-427 from Genentech, which completed a 42-patient Phase 1 trial in 2012. No maximum tolerated dose (MTD) was determined in that study, in which CUDC-427 was administered on a once daily dosing regimen for two weeks followed by one week off treatment. Treatment-related adverse events (AEs) that were Grade 3 or higher in severity were elevated levels of AST and ALT liver enzymes (two patients at 450 and 600 mg doses, respectively) and anemia, fatigue, neutropenia, pruritus, pyrexia and rash (one patient each). AEs that resulted in treatment discontinuation were Grade 3 fatigue in one patient (the only dose limiting toxicity documented on the trial), Grade 2 QTc prolongation, Grade 2 drug hypersensitivity, Grade 2 pneumonitis (one patient each), and Grade 3 pruritus/Grade 2 rash (both AE's in one patient). Unconfirmed complete responses were observed in one patient with ovarian cancer and another patient with MALT lymphoma. A mixed response was observed in one patient with a carcinoma of unknown primary origin. Stable disease lasting longer than three months was observed in four other patients, including one with small cell lung cancer, who remained on study drug for more than 10 months.
A clinical hold is an order issued by FDA to the sponsor of an IND to delay or to suspend a clinical investigation. A clinical hold, including a partial clinical hold, involves the Agency (1) requiring additional information and/or data, (2) reviewing the additional information and/or data, and (3) after the review, informing the sponsor that they can proceed. A partial clinical hold is defined as a delay or suspension of only part of the clinical work requested under the IND (e.g., a specific protocol or part of a protocol is not allowed to proceed; however, other protocols or parts of the protocol are allowed to proceed under the IND).