Phase 1 First-In-Human Trial Of Oral Cudc-907, A Dual Inhibitor Of Pi3k And Hdac, In Patients With Refractory/Relapsed Lymphoma Or Multiple Myeloma

8537 Background: CUDC-907 is an oral inhibitor of class I PI3K as well as class I and II HDAC enzymes. Anti-tumor effects of CUDC-907 have been demonstrated in B-cell lymphoma and multiple myeloma xenografts via inhibition of PI3K, MAPK, and STAT pathways. Methods: In a 3+3 dose escalation and expansion trial, CUDC-907 was administered on 3 dosing schedules: once daily (QD), intermittent (ie, twice [BIW] or thrice [TIW] weekly), or five days on/two days off (5/2) in 21 day cycles. Re-staging was performed every 2 cycles. Results: 45 subjects received CUDC-907 at doses up to 60 mg on the QD or 5/2 schedules, and up to 150 mg on the BIW or TIW schedules. Dose limiting toxicities occurred in 3 subjects: 1 at 60 mg QD (hyperglycemia and diarrhea); 1 at 150 mg BIW (hyperglycemia); and 1 at 150 mg TIW (diarrhea). No DLT occurred on the 5/2 schedule. The most common treatment-related adverse events (AEs) included diarrhea (44%), fatigue (29%), nausea (16%) and thrombocytopenia (11%). 38 subjects are evaluable fo...