Inclusion Criteria:

          -  Ability of participant to understand this study, and participant willingness to sign a
             written informed consent.

          -  Participants must have histologically or cytologically confirmed locally advanced
             unresectable or metastatic urinary bladder (urothelial) cancer. Participants with
             mixed histologies are permitted as long as transitional cell carcinoma is present in
             the pathological specimen.

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension

          -  Documented progression on or within 12 months of treatment with one previous
             platinum-containing regimen or ineligible to receive platinum-containing regimen.
             Neo-adjuvant or adjuvant platinum-based chemotherapy will be deemed to be first-line
             when participants progressed within 12 months of the last dose

          -  Documented progression on prior checkpoint inhibitor or ineligible to receive
             check-point inhibitor

          -  Adequate performance status, organ, and marrow function.

          -  Women of child-bearing potential and men with partners of child-bearing potential must
             agree to practice sexual abstinence, or to use two forms of adequate contraception.

          -  Men of child-bearing potential must not father a child or donate sperm while on this
             study and for 6 months after their last study treatment

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks of
             enrollment/registration.

          -  Current or anticipated use of other investigational agents while participating in this
             study.

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Pregnant or breast feeding (if applicable).

          -  Patients with known brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to TAS 102.

          -  Patients with HIV on anti-retro-viral therapy with thymidine kinase substrates, for
             example, stavudine, zidovudine, telbivudine.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia. Undergoing active treatment for a co-existing malignancy with the
             exception of adequately treated basal cell carcinoma, squamous cell skin cancer,
             thyroid cancer or incidental prostate adenocarcinoma detected at radical cystectomy