FOENIX-CCA3: This phase III trial is trying to understand how safe and effective a targeted therapy drug (futibatinib)is compared to chemotherapy (gemcitabine-cisplatin) as first-line treatment in people with advanced, metastatic or recurrent cholangiocarcinoma with FGFR2 gene rearrangementsA Phase 3, Open-Label, Randomized Study of Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements FOENIX-CCA3

Exclusion

A patient will be excluded from this study if any of the following criteria are met:

1. Patient has received previous systemic anticancer therapy.

   • Patients receiving adjuvant or neoadjuvant treatment and completed ≥6 months prior to randomization are eligible.

2. Patient has mixed hepatocellular carcinoma - iCCA disease.

3. History and/or current evidence of any of the following disorders:

   • Non-tumor related alteration of calcium-phosphorus homeostasis that is clinically significant in the opinion of the Investigator.
   • Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator.
   • Retinal disorder confirmed by retinal examination and considered clinically significant in the opinion of the ophthalmologist.
4. History or current evidence of uncontrolled ventricular arrhythmias
5. Fridericia's corrected QT interval (QTcF) > 470 ms on electrocardiogram (ECG) conducted during Screening.

6. Treatment with any of the following within the specified time frame prior to the first dose of study therapy, or failure to recover from side effects of these prior therapies:

   • Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of study therapy).
   • Radiotherapy (any dose) for extended field within 4 weeks or limited field radiotherapy within 2 weeks, and/or has not recovered from acute impact of radiotherapy.
   • Patients with locoregional therapy, e.g. transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks.
   • Any history of liver transplant.

7. A serious illness or medical condition(s) including, but not limited to, the following:

   • Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month).
   • Known acute systemic infection.
   • Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months.
   • Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the Investigator.
   • Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death.
   • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the Investigator would make the patient inappropriate for entry into this study.
8. Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention.
9. Pregnant or breast-feeding female.
10. The patient is unable to take oral medication.