Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of CUDC-427 When Given to Patients With Advanced and Refractory Solid Tumors or Lymphoma

This is a Phase I, open-label, multicenter, dose-escalation study to evaluate the safety and
tolerability of CUDC-427 as a single agent administered orally, in subjects with advanced
and refractory solid tumors or lymphoma.

Sequential dose escalation cohorts of oral CUDC-427 are planned. Subject enrollment and dose
escalation will proceed according to a standard 3+3 design. In the absence of intolerable
toxicity, each subject will receive a minimum of 1 cycle (21 days) of study treatment, and
may continue to receive additional cycles until disease progression has been documented or
other treatment discontinuation criteria have been met.

No intrasubject dose escalation will be allowed. During the dose escalation phase, up to 3
additional subjects may be enrolled at previously cleared dose levels to better define the
safety, tolerability and activity of the study treatment. Similarly, an MTD expansion cohort
of up to 12 evaluable subjects may also be enrolled.

Safety and tolerability will be assessed by the incidence and severity of adverse events as
assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03). A Safety
Review Committee 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 the Response
Evaluation Criteria in Solid Tumors (RECIST v1.1), or the Revised Response Criteria for
Malignant Lymphoma as appropriate for each subject's tumor type.

Exploratory biological markers of CUDC-427 activity will be assessed in tumor samples (where
available), peripheral blood mononuclear cells (PBMC) and plasma.

Inclusion Criteria:

- Subjects of ≥ 18 years of age.

- Histologically or cytologically confirmed diagnosis of advanced solid tumor or
lymphoma that has progressed following standard therapy or for which there is no
standard or curative therapy.

- Measurable or non-measureable disease.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

- Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments
(excluding alopecia).

- Absolute neutrophil count 1,500/L; platelets 100,000/L; creatinine 1.5x upper limit
of normal (ULN); total bilirubin 1.5x ULN; aspartate aminotransferase/ alanine
aminotransferase (AST/ALT) 2.5x ULN; Tbili liver metastases, the AST/ALT may be 5x ULN.

- Life expectancy of at least 3 months.

- Subjects with adequately treated, stable brain metastases are eligible if
symptomatically controlled on a stable dose of ≤ 10mg prednisone/day or its
equivalent dose of steroids.

- Women of child bearing potential must have a negative serum or urine pregnancy test.

- Men and women of child bearing potential must agree to use adequate birth control
from the time of screening through 30 days after the last dose of study drug.

- Able to provide written informed consent and to follow protocol requirements.

Exclusion Criteria:

- Systemic anticancer therapy within 3 weeks of study entry, except for nitrosoureas or
mitomycin C (6 weeks). Subjects with prostate cancer receiving luteinizing
hormone-releasing hormone (LHRH) hormonal therapy may be enrolled and continue on
this therapy.

- Other investigational agents within 21 days prior to the first dose of study drug.

- Prior treatment with an antagonist of inhibitors of apoptosis proteins.

- History of chronic liver disease, hepatic cirrhosis, current cholestatic disease,
active hepatic infection, non-alcoholic steatohepatitis (NASH), current alcohol or
substance abuse (liver metastases due to disease under study are permitted).

- Pregnant or lactating/breast-feeding women.

- Ongoing treatment with chronic immunosuppressants.

- Known gastrointestinal condition that would interfere with swallowing or the oral
absorption or tolerance of CUDC-427.

- Ongoing diarrhea defined as more than 1 watery stool/day.

- Infection requiring intravenous antibiotic therapy within 14 days prior to the first
dose of study drug.

- Clinically significant cardiac history, such as:

- Uncontrolled or severe cardiovascular disease, including myocardial infarct or
unstable angina within 6 months prior to study treatment, New York Heart
Association (NYHA) Class II or greater congestive heart failure, serious
arrhythmias requiring medication for treatment, clinically significant
pericardial disease, or cardiac amyloidosis.

- Previous history of QTc prolongation as a result of other medication that
required discontinuation of that medication.

- Congenital long QT syndrome or first degree relative with unexplained sudden
death under 40 years of age.

- QTc with Fridericia's (QTcF) correction that is unmeasurable or ≥ 480 msec on
screening ECG. If a subject has a QTcF ≥ 480 sec on the screening ECG, the ECG
may be repeated twice (at least 24 hour apart) and the mean QTcF from the three
screening ECGs must be < 480 msec in order for the subject to be eligible for
the study.

- Ejection fraction (EF) by ECHO < 55% (abnormal values may be repeated x2 and the
mean of the 3 tests used for determination)

- Use of any concomitant medication (within 7 days of starting treatment) that may
cause QTc prolongation, inducing Torsades de Pointes

- Unstable or clinically significant concurrent medical condition that would, in the
opinion of the investigator, jeopardize the safety of a subject and/or their
compliance with the protocol.

- Known human immunodeficiency virus (HIV) positive.

- Prior malignancy within 2 years except non-melanoma skin cancer and other in situ
carcinomas that have been surgically treated with curative intent.