Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements

Inclusion Criteria:

A participant must meet all of the following inclusion criteria to be eligible for enrollment in this study:

1. Provide written informed consent.

2. Is ≥18 years of age (or meets the country's regulatory definition for legal adultage).

3. The participant has histologically confirmed, locally advanced, or metastatic, orrecurrent unresectable iCCA harboring FGFR2 gene rearrangements based on testingperformed by the designated central laboratory.

4. Participant has radiographically measurable disease per RECIST 1.1.

5. Participants who have received treatment for locally advanced disease (for example,trans-arterial chemoembolization, selective internal radiation therapy, externalbeam radiation) must have evidence of radiographic progression with measurabledisease outside the previously-treated lesions.

6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.

7. Adequate organ function as defined by the following criteria:

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×upper limit of normal (ULN); if liver function abnormalities are due tounderlying liver metastasis, AST and ALT ≤ 5 × ULN.

• Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for participants with Gilbert'ssyndrome.

• White Blood Count (WBC) ≥ 2000/mm3 (≥ 2.0 × 109/L)

• Absolute neutrophil count (ANC) ≥ 1000/mm3 (ie, ≥ 1.0 × 109/L by InternationalUnits [IU])

• Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L)

• Hemoglobin ≥ 9.0 g/dL

• Phosphorus ≤ 1.5 × ULN

• Creatinine clearance: ≥ 60 mL/min

8. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy testwithin 7 days prior to administration of the first dose of futibatinib. Femaleparticipants are not considered to be of child bearing potential if they have ahistory of hysterectomy or are post menopausal defined as no menses for 12 monthswithout an alternative medical cause. Both males and females of reproductivepotential must agree to use effective birth control during the study prior to thefirst dose and for 6 months after the last dose.

9. Willing and able to comply with scheduled visits and study procedures.

Exclusion Criteria:

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

1. Participant has received previous systemic anticancer therapy.

•Participants receiving adjuvant or neoadjuvant treatment and completed ≥6 monthsprior to randomization are eligible.

2. Participant 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 isclinically 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 inthe opinion of the Investigator.

• Retinal disorder confirmed by retinal examination and considered clinicallysignificant in the opinion of the ophthalmologist.

4. History or current evidence of uncontrolled ventricular arrhythmias

5. Fridericia's corrected QT interval (QTcF) > 470 milliseconds (ms) onelectrocardiogram (ECG) conducted during Screening.

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

• Major surgery within the previous 4 weeks (the surgical incision should befully healed prior to the first dose of study therapy).

• Radiotherapy (any dose) for extended field within 4 weeks or limited fieldradiotherapy within 2 weeks, and/or has not recovered from acute impact ofradiotherapy.

• Participants 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, thefollowing:

• 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 heartfailure within the previous 6 months.

• Chronic nausea, vomiting, or diarrhea considered to be clinically significantin the opinion of the Investigator.

• Congenital long QT syndrome, or any known history of torsade de pointes, orfamily history of unexplained sudden death.

• Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that in the judgment of the Investigator would make the participantinappropriate for entry into this study.

8. Participants with a history of another primary malignancy that is currentlyclinically significant, and has potential for metastases or currently requiresactive intervention.

9. Pregnant or breast-feeding female.

10. The participant is unable to take oral medication.