A Phase II Nationwide, Fully Decentralized, Telemedicine Study of Pemigatinib in Adult Patients With Advanced or Metastatic Pancreatic Cancer With FGFR2 Gene Fusions or Other FGFR Genetic Alterations

Inclusion Criteria Patients with histologically or cytologically confirmed advanced or metastatic pancreatic cancer of any histologic classification at the time of diagnosis * Written documentation of local or central Clinical Laboratory Improvement Act (CLIA)-certified laboratory determination of FGFR gene fusions/translocations or activating mutations * The study is open to pancreatic cancer in the following cohorts: * Cohort 1: Pancreatic cancer of any histology with FGFR2 fusion/translocation (n, up to 30) who have progressed on or are intolerant to at least one standard of care (SOC) therapy. Prior therapy with a different FGFR inhibitor is not permitted. Patients with concurrent Kirsten rat sarcoma (KRAS) mutations are excluded from this cohort * Cohort 2: Pancreatic cancer of any histology with activating point mutations, fusion/translocation (FGFR1,3,4) extracellular small indels, or kinase domain duplications (n, up to 10). Patients must have progressed on or are intolerant to at least one SOC therapy. Prior therapy with a different FGFR inhibitor is not permitted. Patients with concurrent KRAS mutations are permitted in this cohort * Evidence of measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Patients must have received at least one prior SOC regimen for advanced/metastatic pancreas cancer. Patients should have had evidence of progressive disease following their prior regimen, or if prior treatment was discontinued due to toxicity must have continued evidence of measurable or evaluable disease. Patients who have received prior treatment with an alternate FGFR inhibitor are not eligible for the study * Patients with symptomatic central nervous system (CNS) metastases are excluded (because it is unclear how much CNS penetration the drug has). However, asymptomatic patients with history of successfully treated CNS metastases with surgery or radiation and follow up imaging showing stability, can be eligible * Patients ≥ 18 years of age of either gender * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (patients with ECOG performance status of 2 may be considered on a case-by-case basis after discussion with Incyte) * Able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Ethics Committee (EC) * Recovery from adverse events of previous systemic anti-cancer therapies to baseline or Grade 1, except for: * Alopecia * Stable neuropathy of ≤ Grade 2 due to prior cancer therapy * Able to swallow and retain oral medication * Willing and able to comply with scheduled visits, treatment plan and laboratory tests Exclusion Criteria * Neurological symptoms related to underlying disease requiring increasing doses of corticosteroids. \* Note: Steroid use for management of CNS tumors is allowed but must be at a stable dose for at least 2 weeks preceding study entry * History of another primary malignancy except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study or affect survival * Any other medical condition that would, in the investigator's , prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures * Current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuctivitis, confirmed by ophthalmologic examination * History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral pemigatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) * Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc. * Treatment with any of the following anti-cancer therapies prior to the first dose of pemigatinib within the stated timeframes: * Cyclical chemotherapy (intravenous) within a period of time that is shorter than the cycle length used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin-C) * Biological therapy (e.g., antibodies - including bevacizumab) within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks, whichever is shorter, prior to starting study drug * Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug * Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug * Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug * Patients who are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration are excluded. Patients are not permitted to receive enzyme-inducing anti-epileptic drugs * Consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products within 7 days prior to first dose * Absolute neutrophil count (ANC) ≤ 1,000/mm\^3 \[1.0 x 10\^9/L\] * Platelets ≤ 75,000/mm\^3 \[75 x 10\^9/L\] • Hemoglobin ≤ 9.0 g/dL * Total bilirubin ≥ 1.5x upper limit of normal (ULN) unless associated with patient's primary cancer and/or metastases and with principal investigator's approval * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 3x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval * Alkaline phosphatase ≥ 2.5x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval * Calculated or measured creatinine clearance of \< 40 mL/min * Calcium-phosphate homeostasis: * Inorganic phosphorus outside of institutional normal limits * Total serum calcium (can be corrected) outside of institutional normal limits * 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. Subjects with a pacemaker and well-controlled rhythm for at least 1 month prior to first dose will be allowed * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test * Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment * Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient * Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine systems (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child bearing potential * Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of the study drug and should not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid