- Men and women, ages 18 years or older at the time of signing the informed consent
- Locally advanced or metastatic cholangiocarcinoma with a documented FGFR2 fusion or rearrangement.
- Radiographically measurable disease per Response Evaluation Criteria in Solid Tumors v1.1.
- Documented disease progression or intolerance after at least 1 line of prior systemic therapy
- Willingness to avoid pregnancy or fathering children based on 1 of the following criteria:
- Women of nonchildbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥12 months of amenorrhea)
- Women of childbearing potential who has a negative serum pregnancy test before the first dose and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) until at least 1 month after the last dose of treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the patient and their understanding confirmed
- Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) before the first dose through at least 1 week after the last dose of treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the patient and their understanding confirmed
- Able to provide written informed consent (if needed as per local regulations) and comply with all standard of care visits and procedures.
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- Untreated brain or CNS metastases or brain/CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases). Patients with previously treated and clinically stable brain/CNS metastases and who are off all corticosteroids for ≥ 4 weeks are eligible.
- Are pregnant or lactating.
- Have abnormal laboratory parameters:
- Total bilirubin ≥ 1.5 × upper limit of normal (ULN; ≥ 2.5 × ULN if Gilbert syndrome or disease involving liver)
- Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) > 2.5 × ULN (AST and ALT > 5 × ULN in the presence of liver metastases)
- Creatinine clearance ≤ 30 mL/min based on Cockcroft-Gault
- Serum phosphate > institutional ULN
- Serum calcium outside of the institutional normal range or serum albumin-correct calcium outside of the institutional normal range when serum albumin is outside of the institutional normal range
- History of clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or arrhythmia requiring therapy. Patients with a pacemaker and well-controlled rhythm for at least 1 month prior to first dose will be allowed on therapy
- Have undergone major surgical procedure other than for diagnosis within 28 days of starting treatment
- Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy
- Concurrent anticancer therapy (e.g., chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization)
- Received prior radiation therapy administered within 4 weeks of first dose of pemigatinib. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation to non-CNS disease
- 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
- Use of any potent inhibitors or potent/moderate inducers of CYP3A4. Topical ketoconazole will be allowed
- Known hypersensitivity or severe reaction to pemigatinib or excipients of pemigatinib (refer to the IB).
- Unable or unwilling to swallow pemigatinib or significant gastrointestinal disorder(s) that could interfere with the absorption, metabolism, or excretion.
- Patients with history of hypovitaminosis D requiring supraphysiologic doses to replenish the deficiency. Patients receiving vitamin D food supplements are allowed.
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