Phase I BLASST-3 Trial

Inclusion Criteria: * Written informed consent and any locally-required authorization (e.g. HIPAA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations * Age ≥ 18 years at time of study entry (no safety data in pediatric patients is available for infigratinib). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A). * Histologically confirmed bladder transitional cell carcinoma (TCC) \-- Patients with mixed histology are required to have a component of TCC, and no component of small cell histology * cT2-T4a N0 M0 disease after radiographic staging of chest, abdomen and pelvis, considered appropriate and planned for radical cystectomy as assessed by a Urologic Oncologist. * Presence of the following FGFR3/2 activating alterations, as detected by either plasma or urine cfDNA or cfRNA or by tissue-based NGS (Predicine, Hayward, CA): * Mutations in exon 7 (R248C, S249C) * Mutations in exon 10 (G372C, A393E, Y375C) * Mutations in exon 15 (K652M/T, K652E/Q) * Any FGFR3/2 gene fusion (Availability of baseline archival tumor tissue for identification of FGFR3/2 alterations is not required, but tissue will be obtained when available including either FFPE tumor tissue block or a minimum of fifteen 5μm unstained FFPE slides and fifteen 10μm unstained FFPE slides with an associated pathology report is required) * Ineligibility for cisplatin-based chemotherapy, defined by any of the following: * Creatinine clearance (CL) \<60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-Gault formula. * CTCAE v5.0 Grade \> 1 hearing loss * CTCAE v5.0 Grade \> 1 neuropathy * NYHA Class \> II cardiac dysfunction * Patients not meeting the above criteria are eligible if he/she declines neoadjuvant cisplatin-based chemotherapy after specific informed consent describing the known benefits of cisplatin-based chemotherapy. The reason for cisplatin-ineligibility based on the above criteria or cisplatin refusal should be documented on the case report form. * Adequate organ function laboratory values as defined below: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3) * Platelet count ≥100 x 109/L (\>75,000 per mm3) * International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) \< 1.5 x ULN, unless the patient is receiving anticoagulation therapy provided INR or PTT is within the therapeutic range of the intended anticoagulant therapy. * Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN) \-- This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. * AST (SGOT)/ALT (SGPT) ≤1.5 x institutional upper limit of normal * Measured creatinine CL \>30 mL/min or Calculated creatinine CL\>30 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance: * Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age)/72 x serum creatinine (mg/dL) * Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85/ 72 x serum creatinine (mg/dL) * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following agespecific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). * Patient has ability and willingness to sign a written informed consent document and is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Exclusion Criteria: * Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder * Inoperable tumor(s) with fixation to the pelvic wall on clinical exam * Any previous systemic chemotherapy or radiotherapy for TCC of bladder * Participation in another clinical study with an investigational product during the last 6 months * Any prior participation in a study involving an FGFR inhibitor. * Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study * History of another primary malignancy except for: * Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease (e.g. cervical cancer in situ) * Receipt of the last dose of intravesical chemotherapy or biologic therapy ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG) * Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria * Patients currently receiving treatment with drugs that are known to be strong CYP3A4 inducers or inhibitors, including anti-epileptic drugs. * Use of medications that are known to prolong the QT interval and/or associated with a risk of torsade de pointes 7 days prior to the first dose of infigratinib. * Use of amiodarone within 90 days prior to first dose of infigratinib. * Use of medications that increase serum levels of calcium and/or phosphorus. * Concurrent use of warfarin or other coumadin-derivative anticoagulants; heparin and/or low molecular-weight heparins are permitted. * Inorganic phosphorus and/or total/ionized serum calcium outside normal limits prior to study entry. * Have clinically significant cardiac disease, including any of the following: * New York Heart Association (NYHA) Class ≥2B; subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the NYHA classification. * Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality * Unstable angina pectoris or acute myocardial infarction ≤3 months prior to first dose of study drug * QTcF \>470 msec (males and females). Note: If the QTcF is \>470 msec in the first ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard * Known history of congenital long QT syndrome. * Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable. * Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of infigratinib. NB: local surgery of isolated lesions for palliative intent is acceptable. * History of allogeneic organ transplantation * Current evidence of corneal or retinal disorder/keratopathy * Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent * Female patients who are pregnant or breastfeeding, or patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of infigratinib monotherapy. * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients * Inability to swallow oral medications * Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.