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)
NCT Number: NCT06534983
Acronym: IMCODE004
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Muscle Invasive Urothelial Carcinoma
Interventions: DRUG: Autogene Cevumeran|DRUG: Nivolumab|DRUG: Saline
Sponsor: Hoffmann-La Roche
Collaborators: BioNTech SE
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 362
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-31
Completion Date: 2034-01-06
Locations: Lyell McEwin Hospital; Clinical Trials Unit, Elizabeth Vale, South Australia, 5112, Australia

Summary:
The main purpose of the study is 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 randomization in either autogene cevumeran + nivolumab or the saline + nivolumab arm.

Primary Outcome Measures: Investigator Assessed Disease Free Survival (INV-DFS), Disease recurrence is defined as any of the following:

* Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes)
* Urinary tract recurrence of UC (excluding low-grade non-muscle-invasive bladder cancer (NMIBC))
* Distant metastasis of UC, Randomization until the first recurrence of disease or death from any cause, whichever occurs first (approximately 6 years )
Secondary Outcome Measures: Overall Survival (OS), Randomization until the date of death from any cause (approximately 6 years)|Investigator Assesed DFS in Programmed Death Ligand-1 (PD-L1) Expression ≥ 1% Population, Randomization until first occurrence of a documented disease recurrence or death from any cause, whichever occurs first (approximately 6 years)|Investigator Assessed Distant Metastasis-Free Survival (DMFS), Randomization to the date of diagnosis of distant (i.e., non-locoregional) metastases (approximately 6 years)|Number of Participants with Adverse Events (AEs), Up to approximately 22 months|Change From Baseline in Participant-reported Pain, Physical Function, Role Function and Quality of Life (QoL) as Assessed Using European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30), The EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning scale, three symptom scales, global health status (GHS), QoL, and single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scale scores can be obtained for the multi-item scales. The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much", and the GHS and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent". Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of functioning/quality of life., From Day 1 up to approximately 25 months|Number of Participants With Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE), The PRO-CTCAE contains 124 questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence, severity, and interference with daily function). Treatment toxicities can occur with observable signs (e.g., vomiting) or non-observable symptoms (e.g., nausea). A subset of 16 symptoms (fatigue, chills, nausea, vomiting, diarrhea, constipation, decreased appetite, swelling, itching, rash, headache, muscle pain, joint pain, general pain, cough, and shortness of breath) will be assessed., From Day 1 up to Cycle 21 (cycle length=28 days)|Number of Participants Experiencing AE Burden due to Treatment as Assessed by EORTC Item Library 46 (IL46), The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much"., From Day 8 up to Cycle 21 (cycle length=28 days)|Change from Baseline in Symptomatic Treatment Toxicities as Assessed by National Cancer Institute Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE), The PRO-CTCAE contains 124 questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (0=none to 4=very much) for determination of frequency of occurrence, severity, and interference with daily function. Treatment toxicities can occur with observable signs (e.g., vomiting) or non-observable symptoms (e.g., nausea). A subset of 16 symptoms (fatigue, chills, nausea, vomiting, diarrhea, constipation, decreased appetite, swelling, itching, rash, headache, muscle pain, joint pain, general pain, cough, and shortness of breath) will be assessed in this study., From Day 1 up to Cycle 21 (cycle length=28 days)