|
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 parental consent |
|
|
|
|
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 |
|
|
|
|
|
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 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
|
|
|
|