Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-907 in Patients With Lymphoma or Multiple Myeloma

• To determine the maximum tolerated dose (MTD) or biologically effective dose (BED) and recommended Phase 2 dose (RP2D) of oral CUDC-907 in patients with relapsed or refractory lymphoma or multiple myeloma [ Time Frame: 21 days (1 cycle of study treatment) ]
  Within any given study arm, the highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
  
  

• To assess the safety and tolerability of CUDC-907 [ Time Frame: 18 months ]
  Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
  
  
• To assess pharmacokinetics (PK) of oral CUDC-907 [ Time Frame: Pre-dose to ≥24 hours post-dose on the first and fifteenth day of study drug dosing ]
  Pharmacokinetic parameters will include area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), half-life (T1/2), clearance (Cl) and volume of distribution (Vd).
  
  
• To evaluate biomarkers of CUDC-907 activity [ Time Frame: Day 1, Day 8, and Day 15 of Cycle 1 dosing. ]
  Exploratory biological markers of CUDC-907 activity will be assessed in PBMCs, plasma, skin, hair follicle, tumor and bone marrow samples to explore downstream markers of PI3K and HDAC inhibition and cytokine levels.
  
  
• To assess preliminary anti-cancer activity of CUDC-907 [ Time Frame: 24 months ]
  The Investigator will evaluate each subject for response to therapy according to standard response criteria for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma).
  
  

This is a Phase I, open-label, multi-center dose-escalation trial evaluating the safety and tolerability of CUDC-907 as a single agent administered orally, once daily, to patients with relapsed or refractory lymphoma or multiple myeloma. The following dosing schedules may be examined, all consisting of 21-day cycles and including:

(i) continuous once daily (QD), (ii) twice weekly on Days 1, 4, 8, 11, 15, 18 (BIW) (iii) thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, 19 (TIW) (iv) four days on/three days off on Days 1-4, 8-11, and 15-18 (4/3), and (v) five days on/two days off on Days 1-5, 8-12, and 15-19 (5/2)

Sequential dose escalation cohorts of oral CUDC-907 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design. In the absence of DLT, each subject will be treated for a minimum of 21 days, and may continue to receive additional treatment until disease progression has been documented or other treatment discontinuation criteria have been met.

MTD or BED expansion cohorts of up to 36 evaluable (e.g., up to 12 subjects in each of 2 or 3 specific tumor types or subtype) to better define the safety, tolerability and preliminary antitumor and pharmacodynamic activity of the study treatment, as well as suitability as an RP2D and schedule.

Safety and tolerability will be assessed by the incidence and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety Review Committee (SRC) comprised of the Medical Monitor, Principal Investigators, and Sponsor representatives, will be convened to review safety information and to decide upon dose escalation and further subject enrollment.

The antitumor activity of study treatment will be assessed according to standard response criteria as appropriate for each individual subject's tumor type (e.g., Revised Response Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple Myeloma).

Exploratory biological markers of activity will be assessed in peripheral blood mononuclear cells (PBMC), plasma and tissue specimens (skin, tumor and bone marrow samples, where available).