Background: Despite surgical resection and the use of neoadjuvant or adjuvant chemotherapy, up to 50% of patients with invasive urothelial carcinoma experience disease recurrence and eventually die of metastatic disease. New therapeutic approaches are needed for these patients. Approximately 50% of patients with pathologic high risk features have evidence of HER2 expression on the primary tumor or involved lymph nodes. DN24-02 is an autologous cellular immunotherapy targeting HER2, and is based on the same platform as sipuleucel-T, which was approved by FDA in 2010 for treatment of men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Each dose of DN24-02 is manufactured by culture of peripheral blood mononuclear cells (PBMCs) obtained by leukapheresis with the recombinant antigen BA7072, which comprises components of the intra- and extracellular domains of the HER2 antigen linked to GM-CSF. A product similar to DN24-02 has demonstrated evidence of safety and immune response in phase I studies. The primary objective is to determine whether DN24-02 given as adjuvant therapy following surgical resection can prolong survival compared to the control group. Secondary objectives are to evaluate disease-free survival, safety, and immune responses to DN24-02. Methods: Eligible patients will have undergone surgical resection of a primary urothelial cancer, with either ≥pT2 or pN+ staging, and HER2 expression ≥ 1+ by IHC based on pathologic review. Up to 180 subjects will be randomized (1:1) to receive DN24-02 as adjuvant therapy approximately every 2 weeks, given as IV infusions 3 times, or standard of care. Stratification will include 1) neoadjuvant chemotherapy vs. surgery alone; and 2) positive (pN+) vs. negative lymph node involvement (pN0). Adjuvant chemotherapy will not be allowed. Patients can be treated per standard of care if there is disease recurrence. Patients will be monitored for evidence of disease recurrence by imaging, and will be followed for survival. Cellular and serological immune responses will be assessed at baseline and post-DN24-02 therapy.