Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)

Inclusion Criteria:

* Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
* Measurable disease by CT or MRI as defined by RECIST v1.1
* Disease progression or recurrence after treatment:
* i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
* ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
* Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
* Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Blood sample must be provided for mMDSC levels for randomization into the study

Exclusion Criteria:

* Active brain metastases or leptomeningeal metastases
* Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
* Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
* Active, known, or suspected autoimmune disease
* A condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
* Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
* Prior surgery or gastrointestinal dysfunction that may affect drug absorption
* Past medical history of interstitial lung disease
* History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
* Positive test for hepatitis B, C or HIV
* Dependent on continuous supplemental oxygen