A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran With Nivolumab Versus Nivolumab Alone in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC)

Open to people ages 18 years and up

• Participants must have the capacity to participate/enroll in the study and to provide informed consent
• Histologically confirmed muscle-invasive UC (also termed TCC) of the bladder or upper urinary tract
• TNM classification (UICC/AJCC 7th edition) at pathological examination of surgical resection specimen of (y)pT3-4 or (y)pN+ and M0
• Surgical resection of MIUC of the bladder or upper tract
• Participants who have not received prior neoadjuvant cisplatin chemotherapy (NAC) must be ineligible to receive adjuvant cisplatin therapy due to participant refusal, cisplatin ineligibility or investigator decision
• Tumor tissue must be provided for biomarker analysis
• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization.
• Full recovery from cystectomy or nephroureterectomy within 120 days following surgery
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HbsAg) test at screening
• Positive hepatitis B surface antibody (HBsAb), or a negative HBsAb at screening accompanied by either of the following: negative total hepatitis B core antibody (HBcAb) or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 international units/milliliter (IU/mL)
• Negative hepatitis C virus (HCV) antibody test at screening, or a positive HCV antibody test followed by a negative HCV RNA test at screening

• Partial cystectomy in the setting of bladder cancer primary tumor or partial nephroureterectomy in the setting of renal pelvis primary tumor
• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
• Any prior neoadjuvant immunotherapy
• Adjuvant chemotherapy or radiation therapy for UC following surgical resection
• Malignancies other than UC within 5 years prior to randomization
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment