Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment
2. Histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra.
3. Prior anti-PD-(L)1 treatment.
4. Measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or MRI.
5. Recurrent disease after any prior platinum-based chemotherapy regimen or ineligible for platinum therapy.
6. Adequate organ and marrow function as defined
7. Must have a life expectancy of at least 12 weeks.
8. Body weight > 30 kg

Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria

Exclusion Criteria:

1. History of allogeneic organ transplantation.
2. Active or prior documented autoimmune or inflammatory disorders
3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure .
4. History of another primary malignancy
5. History of leptomeningeal carcinomatosis.
6. History of active primary immunodeficiency.
7. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus .