Pemigatinib before Surgery for the Treatment of Recurrent Low- or Intermediate Risk Non-Muscle Invasive Bladder Cancer

Inclusion Criteria

• Prior histologically confirmed low- or intermediate-risk non-muscle invasive urothelial carcinoma of the bladder (NMIBC) defined by: * Low-risk group: Initial tumor with all of the following: ** Solitary tumor ** Ta tumor ** Low-grade ** < 3 cm ** No carcinoma in situ (CIS) * Intermediate-risk group: ** All tumors not defined in the two adjacent categories (between the category of low- and high-risk) * High-risk group: Any of the following: ** T1 tumor ** High-grade ** CIS ** Multiple and recurrent and large ( > 3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors)
• Documented tumor recurrence as noted in standard of care follow up cystoscopy
• Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance status 0-2
• White blood cell count (WBC) >= 3.0 K/mm^3
• Absolute neutrophil count (ANC) >= 1.5 K/mm^3
• Platelets >= 100 K/mm^3
• Hemoglobin (Hgb) >= 9 g/dL
• Serum total bilirubin =< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN
• Serum calcium =< ULN
• Serum phosphate =< ULN
• Serum creatinine =< 1.5 x ULN or serum creatinine > 1.5 – 3 x ULN if calculated creatinine clearance (CrCl) is >= 30 mL/min using the modified Cockcroft-Gault equation
• Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria

• Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) high-grade urothelial carcinoma of any T-stage * NOTE: Patients with histologically confirmed concurrent upper urinary tract non-invasive low-grade urothelial carcinoma may be considered for enrollment after consultation with the study chair
• Patients with high grade urothelial carcinoma on their most recent urine cytology
• Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment
• Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies =< 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received prior selective fibroblast growth factor receptor targeting agents (i.e. pemigatinib, dovitinib, BGJ398, AZD4547, JNJ-42756493, etc.)
• Patients who have had radiotherapy =< 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device =< 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: * Clinically significant cardiac diseases, including any of the following: ** History or presence of serious uncontrolled ventricular arrhythmias ** Clinically significant resting bradycardia ** Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE) ** Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication(s) * Active impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of pemigatinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * Cirrhosis, chronic active hepatitis or chronic persistent hepatitis * Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) * Patients who are currently receiving anti-coagulation treatment with therapeutic doses of warfarin. Full-dose anti-coagulation with low molecular weight heparin is permitted. * Patients with a prior history of significant ocular pathology including but not limited to detached retina, retinal vein/artery occlusion, macular degeneration, or glaucoma. Patients with prior history of cataracts are permitted to enroll. * Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol * 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 tendon or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
• Pregnant or breast-feeding women
• Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 14 days prior to starting study drug
• Fertile males not willing to use contraception, as stated above
• Patients unwilling or unable to comply with the protocol