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) (IMCODE004)

August 5, 2026 updated by: Hoffmann-La Roche

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma Buenos Aires, Argentina, C1199ABB
        • Hospital Italiano
  • Australia
    • South Australia
      • Elizabeth Vale, South Australia, Australia, 5112
        • Lyell McEwin Hospital
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Center
  • Denmark
      • Aalborg, Denmark, 9000
        • Aalborg Universitetshospital
      • Aarhus N, Denmark, 8200
        • Aarhus Universitetshospital
      • Herlev, Denmark, 2730
        • Herlev Hospital
  • Germany
      • Berlin, Germany, 10967
        • Vivantes Klinikum am Urban
      • Heidelberg, Germany, 69120
        • Uniklinikum Heidelberg
      • Herne, Germany, 44625
        • Marien Hospital Herne
      • Stuttgart, Germany, 70174
        • Klinikum Stuttgart - Katharinenhospital
  • Greece
      • Athens, Greece, 124 61
        • Attikon University General Hospital
      • Thessaloniki, Greece, 546 39
        • Theageneio Hospital
  • Italy
    • Apulia
      • Bari, Apulia, Italy, 70124
        • A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
    • Lazio
      • Rome, Lazio, Italy, 00144
        • IFO - Istituto Regina Elena
    • Piedmont
      • Orbassano, Piedmont, Italy, 10043
        • A.O. Universitaria S. Luigi Gonzaga
    • Veneto
      • Verona, Veneto, Italy, 37134
        • A.O.U di Verona Policlinico G.B. Rossi
  • Norway
      • Lørenskog, Norway, 1474
        • Akershus Universitetssykehus
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
      • Olsztyn, Poland, 10-228
        • Szpital Kliniczny Ministerstwa Spraw Wewn?trznych i Administracji z Warmi?sko-Mazurskim Centrum Onkologii w Olsztynie
      • Skórzewo, Poland, 60-185
        • AIDPORT Sp. z o. o.
  • South Korea
      • Seongnam-si, South Korea, 463-707
        • Seoul National University Bundang Hospital
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 05505
        • Asan Medical Center
      • Seoul, South Korea, 06351
        • Samsung Medical Center
  • Spain
      • Madrid, Spain, 28040
        • Hospital Clínico San Carlos
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocío
      • Zaragoza, Spain, 50009
        • Hospital Clínico Universitario Lozano Blesa
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
        • ICO l'Hospitalet
      • Sant Andreu de la Barca, Barcelona, Spain, 08740
        • Vall d'Hebron Institute of Oncology (VHIO), Barcelona
  • Sweden
      • Gothenburg, Sweden, 413 45
        • Sahlgrenska University hospital
  • Taiwan
      • Kaohisung, Taiwan, DUMMY_VALUE
        • Chang Gung Medical Foundation - Kaohsiung
  • United Kingdom
      • Exeter, United Kingdom, EX2 5DW
        • Royal Devon and Exeter Hospital
      • London, United Kingdom, EC1M 6BQ
        • Barts & London School of Med;Medical Oncology
  • United States
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Cancer Center Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • MSK Monmouth
      • Montvale, New Jersey, United States, 07645
        • MSK Bergen
    • New York
      • Commack, New York, United States, 11725
        • MSK Commack
      • Harrison, New York, United States, 10604
        • MSK Westchester
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Uniondale, New York, United States, 11553
        • MSK Nassau
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autogene Cevumeran + Nivolumab
Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints.
Drug: Autogene Cevumeran
Autogene cevumeran will be administered as an IV infusion per the schedule specified in the arm.
Other Names:
  • RO7198457
Drug: Nivolumab
Nivolumab will be administered as an IV infusion per the schedule specified in the arm.
Other Names:
  • Opdivo
Active Comparator: Nivolumab
Participants will receive 480 milligrams (mg) of nivolumab, IV, once every 4 weeks (Q4W) for 1 year.
Drug: Nivolumab
Nivolumab will be administered as an IV infusion per the schedule specified in the arm.
Other Names:
  • Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Adverse Events (AEs)
Time Frame: Up to approximately 15 months
Up to approximately 15 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Randomization until the date of death from any cause (approximately 6 years)
Randomization until the date of death from any cause (approximately 6 years)
Number of Participants Experiencing AE Burden due to Treatment as Assessed by EORTC Item Library 46 (IL46)
Time Frame: From Day 8 up to Cycle 21 (cycle length=28 days)
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)
INV-DFS in Programmed Death Ligand-1 (PD-L1) Expression ≥ 1% Population
Time Frame: Randomization until first occurrence of a documented disease recurrence or death from any cause, whichever occurs first (approximately 6 years)
Randomization until first occurrence of a documented disease recurrence or death from any cause, whichever occurs first (approximately 6 years)
INV-Distant Metastasis-free Survival (DMFS)
Time Frame: Randomization to the date of diagnosis of distant (i.e., non-locoregional) metastases (approximately 6 years)
Randomization to the date of diagnosis of distant (i.e., non-locoregional) metastases (approximately 6 years)
Number of Participants With Adverse Events (AEs)
Time Frame: Up to approximately 22 months
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-C30 (EORTC QLQ-C30)
Time Frame: From Day 1 up to approximately 25 months
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/QoL.
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)
Time Frame: From Day 1 up to Cycle 21 (cycle length=28 days)
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)
Change from Baseline in Symptomatic Treatment Toxicities as Assessed by NCI PRO-CTCAE
Time Frame: From Day 1 up to Cycle 21 (cycle length=28 days)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Collaborators

BioNTech SE

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 9, 2024

Primary Completion (Estimated)

November 10, 2027

Study Completion (Estimated)

November 10, 2027

Study Registration Dates

First Submitted

July 30, 2024

First Submitted That Met QC Criteria

July 30, 2024

First Posted (Actual)

August 2, 2024

Study Record Updates

Last Update Posted (Actual)

August 6, 2026

Last Update Submitted That Met QC Criteria

August 5, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BO45230
  • 2023-509023-40-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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