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