Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder

In Part A, escalating doses of DKN-01 will be administered to different cohorts of patients
to evaluate safety and dose limiting toxicities (DLTs) and to establish the maximum tolerated
dose of DKN-01 when administered in combination with gemcitabine and cisplatin.

Part B is an expansion cohort in which patients are treated at the MTD of DKN-01 (or highest
dose tested if the MTD is not defined) to further characterize safety, tolerability,
pharmacokinetics and efficacy within the defined patient population.

Inclusion Criteria:

1. Patient has carcinoma primary to the intra- or extra-hepatic biliary system or gall
bladder.

2. Patient must have sufficient tumor tissue available for submission.

3. For patients who have received prior cryotherapy, radiofrequency ablation,
radioembolization, ethanol injection, transarterial chemoembolization (TACE) or
photodynamic therapy, at least 28 days must have elapsed since that therapy, and
lesions that have not been treated with local therapy must be present and measurable.

4. Patients may have received prior adjuvant chemotherapy with gemcitabine with or
without cisplatin, as long as 6 months have elapsed since last treatment.

5. Patients must have one or more tumors measurable on radiographic imaging as defined by
RECIST.

6. ECOG PS of 0 or 1. Patients with an ECOG PS of 2 may be entered upon review and
approval of the medical monitor.

7. Estimated life expectancy of at least 3 months.

8. Disease-free of active second/secondary or prior malignancies for ≥ 2 years with the
exception of currently treated basal cell or squamous cell carcinoma of the skin, or
carcinoma in-situ of the cervix or breast.

9. Adequate hematological, renal, hepatic and coagulation laboratory test results.

10. Women of child bearing potential and men must agree to use adequate contraception
during the study and for 6 months after their last dose of study drug.

11. Available for the duration of the study and are willing to follow study-specific
procedures.

12. Provide written informed consent

Exclusion Criteria:

1. New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months, or unstable arrhythmia.

2. Have Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or
history of congenital long QT syndrome.

3. Active, uncontrolled bacterial, viral, or fungal infections.

4. Known to be human immunodeficiency virus (HIV) positive or has untreated, active
hepatitis B.

5. History of major organ transplant.

6. History of an autologous/allogenic bone marrow transplant.

7. Serious nonmalignant disease.

8. Pregnant or nursing.

9. History of osteonecrosis of the hip or have evidence of structural bone abnormalities
in the proximal femur on MRI scan that are symptomatic and clinically significant.

10. Symptomatic central nervous system (CNS) malignancy or metastasis.

11. Clinically significant peripheral neuropathy

12. Known osteoblastic bony metastasis.

13. Treatment with surgery or chemotherapy within 21 days prior to study entry or
radiation within 14 days of study entry.

14. Previously treated with an anti-Dkk-1 therapy.

15. Other exclusions apply