Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

Key Inclusion Criteria

• Signed written informed consent granted prior to initiation of any study-specific procedures
• 18 years of age or older
• Histologically or cytologically confirmed locally advanced, inoperable, or metastatic iCCA or mixed histology tumors
• Substudy 1:

FGFR2 fusion status based on the following assessments:

a) If central laboratory was designated by Sponsor: Positive FISH test; and/or b) If non-central laboratory: i) Positive FISH or NGS test: patients were potentially enrolled and started dosing, but central confirmation was required* ii) Negative FISH or NGS test: tissue was submitted to the central laboratory designated by the Sponsor, and patients were only enrolled in case the central test was positive

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

Substudy 2:

FGFR2 mutation/amplification status based on local NGS testing performed or commissioned by the respective study site.

• Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression
• Measurable disease by RECIST version 1.1 criteria
• ECOG performance status ≤ 1
• 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 10^9/L
• Platelet count ≥ 75 x 109/L
• International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for subjects who received 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 ≥ 30 mL/min as estimated by the Cockcroft-Gault equation
• Female and male patients of child-producing potential must had agreed to avoid becoming pregnant or impregnating a partner, respectively, used double-barrier contraceptive measures, oral contraception, or had to avoid of intercourse, during the study, and until at least 120 for 90 days after the last dose of derazantinib.

Male or female patients of child-producing potential must had agreed to comply with one of the following until at least 120 days after the last dose of derazantinib:

• Abstinence from heterosexual activity
• Using (or having their partner use) an acceptable method of contraception during heterosexual activity.

Key Exclusion Criteria

• Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
• One chemotherapy or biological (e.g., antibody) cycle interval
• Five half-lives of any small-molecule investigational or licensed medicinal product
• Two weeks, for any investigational medicinal product with an unknown half-life
• Four weeks of curative radiotherapy
• Seven days of palliative radiotherapy
• 28 days of radiotherapy
• Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib
• Previous treatment with any FGFR inhibitor (e.g., Balversa® [erdafitinib], Pemazyre® [pemigatinib], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).
• Patients who were unable or unwilling to swallow the complete daily dose of derazantinib capsules
• Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must had stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or had CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
• Evidence of clinically significant corneal or retinal disorder which was likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion, infl