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)

Inclusion criteria

• Participants must have the capacity to participate/enroll in the study and to provide informed consent
• Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma [TCC]) of the bladder or upper urinary tract
• Tumor-node-metastasis (TNM ) classification (Union for International Cancer Control [UICC]/American Joint Committee on Cancer [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 received neoadjuvant chemotherapy (NAC), including antibody drug-conjugate, either alone or in combination with a checkpoint inhibitor (CPI), are eligible
• Participants who have not received any prior NAC are also eligible, provided they meet one of the following criteria, which would make them ineligible to receive adjuvant cisplatin-based therapy: 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 human immunodeficiency virus (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) deoxyribonucleic acid (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 ribonucleic acid (RNA) test at screening

Exclusion criteria

• 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
• Adjuvant chemotherapy, immunotherapy, or radiation therapy for UC following surgical resection
• Prior active malignancies within 3 years prior to randomization
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment