A Study of ABC294640 (Yeliva ®) in the Treatment of Patients With Advanced Cholangiocarcinoma

This is an open label clinical study to explore the activity signal of ABC294640 in adult
subjects who have been diagnosed with unresectable cholangiocarcinoma either intra- perhilar
or extra-hepatic.

A maximum of 39 participants evaluable for efficacy will be enrolled in the study which will
be conducted at up to 5 sites in the USA. Eligible participants will receive ABC294640, 500
mg twice a day, continuously administered in 28 day cycles.

In addition to physical and neurological exams, blood and urine samples will be routinely
collected for safety and to determine response to the study drug. Participants will be
radiographically assessed for disease status every 2 cycles of treatment.

Tumor biopsies, when accessible, will be obtained within 21 days prior to the beginning of
treatment and again on the beginning of the second treatment cycle.

All participants will be followed every 2 months for progression and survival for a maximum
of 24 months after the last patient has been entered to the study. Follow up procedures may
include physical examination, laboratory work and radiographic tumor assessment.

Inclusion Criteria:

1. Patients with histologically confirmed intrahepatic, perihilar or extra-hepatic CCA.

2. Patients with no more than 2 prior treatments with systemic anti-neoplastic therapy
for CCA.

3. The tumor is unresectable and not amenable to curative therapy.

4. One or more tumors measurable on CT scan per RECIST 1.1.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0- 1.

6. Life expectancy of at least 3 months.

7. Age ≥18 years.

8. Signed, written IRB-approved informed consent.

9. A negative pregnancy test (if female).

10. Acceptable liver and renal function:

- Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 2 baseline)

- AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal (ULN),

- Serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)

- Albumin > 3.0 g/dL

11. Acceptable hematologic status:

- Absolute neutrophil count ≥1000 cells/mm3

- Platelet count ≥75,000 (plt/mm3) (CTCAE Grade 1 baseline)

- Hemoglobin ≥ 9 g/dL

12. Acceptable blood sugar control:

- Fasting glucose value ≤ 160 mg/dL (CTCAE Grade 1 baseline)

13. Urinalysis: No clinically significant abnormalities.

14. Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 X ULN after
correction of nutritional deficiencies that may have contributed to prolonged PT/PTT.

15. For men and women of child-producing potential, willingness to use effective
contraceptive methods during the study. If female (or female partner of male patient),
was either not of childbearing potential (defined as postmenopausal for ≥ 1 year or
surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy])
or practicing one of the following medically acceptable methods of birth control and
agreed to continue with the regimen throughout the duration of the study:

- Oral, implantable or injectable contraceptives for 3 consecutive months before
the baseline/randomization visit.

- Total abstinence from sexual intercourse (≥ 1 complete menstrual cycle before the
baseline/randomization visit).

- Intrauterine device.

- Double barrier method (condoms, sponge, diaphragm or vaginal ring with
spermicidal jellies or cream

Exclusion Criteria:

1. >2 previous systemic anti-neoplastic regimens for CCA.

2. New York Heart Association Class III or IV, cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.

3. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy.

4. Pregnant or nursing women. NOTE: If a woman became pregnant or suspects she is
pregnant while participating in this study, she must inform her treating physician
immediately.

5. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy
within 28 days prior to study entry.

6. Patients who have received any antineoplastic therapy > 28 days prior to starting
treatment with ABC294640 and have not adequately recovered from side effects and
toxicities of previous antineoplastic therapy.

7. Unwillingness or inability to comply with procedures required in this protocol.

8. Known infection with human immunodeficiency virus.

9. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
investigator and/or the sponsor.

10. Patients who were currently receiving any other investigational agent.

11. Patients who were receiving drugs that were sensitive substrates of CYP450 1A2, 3A4,
2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that
could not have been stopped at least 7 days or 5 half-lives (whichever was longer)
before starting treatment with ABC294640, could not have been replaced with another
appropriate medication or not given for the duration of the clinical study. (A list of
commonly used drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or
2D6, or strong inhibitors or inducers of all major CYP450 isozymes with the half-life
of each drug identified, is included in Appendix 3)

12. Patients who are taking Coumadin or Coumadin derivatives.