A Randomized Phase II, Double-blind, Multicenter Study Evaluating the Efficacy and Safety of Autogene Cevumeran Plus Nivolumab Versus Nivolumab as Adjuvant Therapy in Patients With High-risk Muscle-invasive Urothelial Carcinoma
The original purpose of this study was to evaluate the efficacy of adjuvant treatment with autogene cevumeran plus nivolumab compared with nivolumab in participants with high risk MIUC. In this study participants will be enrolled in a safety run-in phase to receive autogene cevumeran + nivolumab. This phase will be conducted to monitor and ensure the safety of study participants. After all participants in the safety run-in have been enrolled to receive autogene cevumeran + nivolumab, further participants will be randomized in either autogene cevumeran + nivolumab or the nivolumab monotherapy arm. Following the Sponsor's decision to phase out the study, as of Protocol Version 5, the primary purpose of the study is to ensure treatment continuity and safety for the participants who continue to participate in the study and receive study treatment.
• 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