The purpose of this study is to evaluate the efficacy and safety of pemigatinib versus
gemcitabine plus cisplatin chemotherapy in first-line treatment of participants with
unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.
- Male and female participants at least 18 years of age at the time of signing the
informed consent form (ICF); a legally minor participant from Japan needs written
- 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
- Eastern Cooperative Oncology Group performance status 0 to 1.
- Documented FGFR2 rearrangement.
- Willingness to avoid pregnancy or fathering children.
- 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).
- 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.
- Must not be 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).
- Gastrointestinal conditions/disorders that may raise gastric and/or small intestinal
pH 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
- Chronic or current active infectious disease requiring systemic antibiotics,
antifungal or antiviral treatment within 2 weeks prior to enrollment.
- Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives
(whichever is longer) before the first dose of study treatment.
- Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or
- Inadequate recovery from toxicity and/or complications from a major surgery before