Derazantinib in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

Inclusion Criteria:

1. Signed written informed consent granted prior to initiation of any study-specific
procedures

2. 18 years of age or older

3. Histologically or cytologically confirmed locally advanced, inoperable (where surgery
is not indicated due to disease extension, co-morbidities, or other technical
reasons), or metastatic iCCA or mixed histology tumors (combined
hepatocellular-cholangiocarcinoma [cHCC-CCA])

4. FGFR2 gene fusion status based on the following assessments:

1. If central laboratory designated by Sponsor:

Positive FISH test; and/or

2. If non-central laboratory:

i) Positive FISH or NGS test: patients may be enrolled and may start dosing, but
central confirmation is required*

ii) Negative FISH or NGS test: tissue may be submitted to the central laboratory
designated by the Sponsor, and patients may only be enrolled if the central test is
positive

*Using standard protocols and approved by local IRB/EC, by CLIA or other similar
agency.

5. Received at least one regimen of prior systemic therapy and then experienced
documented radiographic progression or was not able to tolerate prior systemic
therapy.

- If the subject received at least 4 cycles of systemic therapy and no measurable
tumor reduction compared to the previous scan is observed, such subject can be
enrolled

- If the subject received immunotherapy, the documented radiographic disease
progression is required

6. Measurable disease by RECIST version 1.1 criteria

7. ECOG performance status ≤ 1

8. Adequate organ functions as indicated by the following laboratory values (based on
screening visit values from the central laboratory).

- Hematological

- Hemoglobin (Hgb) ≥ 9.0 g/dL

- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

- Platelet count ≥ 75 x 109/L

- International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤
3 for subjects receiving anticoagulant therapy such as Coumadin or heparin

- Hepatic

- Total bilirubin ≤ 2 x ULN

- AST and ALT ≤ 3 ULN (≤ 5 x ULN for subjects with liver metastases)

- Albumin ≥ 2.8 g/dL

- Renal

- Serum creatinine ≤ 1.5 x ULN

- Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault
equation

9. Male or female subjects of child-producing potential must agree to use double-barrier
contraceptive measures, oral contraception, or avoidance of intercourse during the
study and for 90 days after the last dose of derazantinib

Exclusion Criteria:

1. Systemic anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted
therapy, or investigational agents within four weeks of the first dose of derazantinib

2. Major surgery, locoregional therapy, or radiation therapy within four weeks of the
first dose of derazantinib

3. Previous treatment with any FGFR inhibitor (e.g., ponatinib, dovitinib, nintedanib,
AZD4547, NVP-BGJ398, LY2784455, BAY1163877)

- Subjects who received less than four weeks of therapy and were unable to continue
therapy due to toxicity will be allowed to participate

4. Unable or unwilling to swallow the complete daily dose of derazantinib capsules

5. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects
must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or
computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose
steroids, anti-epileptics, or other symptom-relieving medications)

6. Current evidence of corneal or retinal disorder, including but not limited to
bullous/band keratopathy, keratoconjunctivitis, corneal abrasion,
inflammation/ulceration, confirmed by ophthalmologic examination

7. Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing
complications after laparoscopic procedures or stent placement, including but not
limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to
be treated and disorders/complications should be resolved within 2 weeks prior to the
first dose of derazantinib)

8. History of significant cardiac disorders:

- Myocardial infarction (MI) or congestive heart failure defined as Class II to IV
per the New York Heart Association (NYHA) classification within 6 months of the
first dose of derazantinib (MI that occurred > 6 months prior to the first dose
of derazantinib will be permitted)

- QTcF >500 msec (males or females)

9. Significant gastrointestinal disorder(s) that could, in the opinion of the
Investigator, interfere with the absorption, metabolism, or excretion of derazantinib
(e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)

10. Previous malignancy within 2 years of the first dose of derazantinib, except
curatively treated or low grade malignancies such as non-melanoma skin cancer,
carcinoma in-situ of the breast, cervix, and superficial bladder tumors

11. Concurrent uncontrolled illness not related to cancer, including but not limited to:

- Psychiatric illness/substance abuse/social situation that would limit compliance
with study requirements

- Known uncontrolled human immunodeficiency virus (HIV) infection

12. Blood or albumin transfusion within 5 days of the blood draw being used to confirm
eligibility

13. Pregnant or breast feeding