Phase 1, Open-label Trial to Determine Safety of OPB-51602 in Subjects With Advanced Cancer

This study is based on data that support a role for the signal transducer and activator of
transcription (STAT) family of proteins in oncogenesis. One of the mechanisms of action of
OPB-51602 includes inhibition of STAT3 phosphorylation. Therefore OPB-51602 is expected to
be active as an anti-cancer drug. This first-in-human study will characterize the safety
profile of OPB-51602, evaluate the pharmacokinetics of OPB-51602, identify a recommended
phase II dose, and obtain preliminary efficacy data, in subjects with advanced cancers for
whom there is no standard treatment available.

Inclusion Criteria:

1. Male or female subjects aged ≥ 18 years

2. Pathologically confirmed advanced cancer that is resistant or refractory to standard
therapy or for which no standard curative therapy is available

3. At least 4 weeks since the last dose of prior chemotherapy, radiation therapy, or
investigational agent.

4. Subjects must have recovered from adverse effects of prior therapy at time of
enrollment to ≤ Grade 1 (excluding alopecia)

5. ECOG performance status ≤ 1

6. Life expectancy of ≥ 3 months following study entry

7. Adequate organ function, defined as follows:

- Serum creatinine < 1.5 x the upper limit of normal (ULN)

- Aspartate aminotransferase and alanine aminotransferase levels ≤ 3.0 x ULN (≤
5.0 x ULN in the presence of known liver metastasis)

- Total bilirubin ≤ 1.5 x ULN

- Alkaline phosphatase levels ≤ 2.5 x ULN (≤ 5 x ULN in presence of bone
metastasis)

- Absolute neutrophil count of ≥ 1,500/mm³ (≥ 1.5 x 10⁹/L)

- Platelet count ≥ 100,000/mm³ (≥ 100 x10⁹/L)

- Hemoglobin ≥ 9 g/dL

8. For women of childbearing potential (WOCBP), a negative serum pregnancy test result
at screening and negative urine pregnancy test on Day 1

9. WOCBP or men whose sexual partners are WOCBP must agree to use 2 methods of adequate
contraception

10. Before any protocol-specific screening procedures are performed, subjects must have
signed and dated the IRB-approved ICF.

Exclusion Criteria:

1. Uncontrolled concurrent illness, including ongoing or active infection, uncontrolled
hypertension,or any other condition that could raise the subject's safety risk.

2. Altered mental status, psychiatric illness, or social situation that could limit
compliance with study requirements and/or confound interpretation of study results.

3. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C.

4. Known brain metastasis that has not been treated and stable for at least 4 weeks, or
subjects with leptomeningeal disease.

5. Subjects unable to swallow oral medications or with pre-existing gastrointestinal
disorders that might interfere with absorption of oral drugs.

6. A history of major surgery within 28 days of first receipt of study drug. Subjects
must have recovered fully from any surgery.

7. Nursing or pregnant women

8. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that, in opinion of investigator, contraindicates use of an
investigational drug, or that may render subject at excessively high risk for
treatment complications.