A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma

Inclusion Criteria

• Male and female participants at least 18 years of age at the time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed cholangiocarcinoma that is previously untreated and considered unresectable and/or metastatic (Stage IV per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual).
• Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group performance status 0 to 1.
• Documented FGFR2 rearrangement.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria

• Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant received 1 cycle of gemcitabine plus cisplatin [the start of study drug {Cycle 1 Day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin]).
• Child-Pugh B and C.
• Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening.
• Concurrent anticancer therapy, other than the therapies being tested in this study.
• Participant is a candidate for potentially curative surgery.
• Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
• Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment.
• Known central nervous system (CNS) metastases or history of uncontrolled seizures.
• Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
• Laboratory values at screening outside the protocol-defined range.
• History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance).
• Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib.
• Clinically significant or uncontrolled cardiac disease.
• History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful.
• Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months.
• Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
• Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.