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)

NCT06534983 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: BO452302023-509023-40-00
• Study Type: interventional
• Target: 362
• Locations: 20 countries
• Sites: 107

Brief 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 randomized in either autogene cevumeran + nivolumab or the saline + nivolumab arm.

Conditions

Muscle-invasive Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Investigator-assessed (INV) Disease-free Survival (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 Outcomes (8)

• Overall Survival (OS)

  Randomization until the date of death from any cause (approximately 6 years)

• INV-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)

• INV-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-C30 (EORTC QLQ-C30)

  From Day 1 up to approximately 25 months

Study Arms (2)

Autogene Cevumeran + Nivolumab

EXPERIMENTAL

Participants will receive autogene cevumeran along with nivolumab intravenously (IV) at a recommended dose at specified timepoints.

Drug: Autogene Cevumeran; Drug: Nivolumab

Saline + Nivolumab

ACTIVE COMPARATOR

Participants will receive saline solution along with 480 milligrams (mg) of nivolumab, IV, once every 4 weeks (Q4W) for 1 year.

Drug: Nivolumab; Drug: Saline

Interventions

Autogene Cevumeran DRUG

Autogene cevumeran will be administered as an IV infusion per the schedule specified in the arm.

Also known as: RO7198457

Autogene Cevumeran + Nivolumab

Nivolumab DRUG

Nivolumab will be administered as an IV infusion per the schedule specified in the arm.

Also known as: Opdivo

Autogene Cevumeran + Nivolumab; Saline + Nivolumab

Saline DRUG

Saline solution for IV infusion.

Saline + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• BioNTech SE: collaborator

Study Sites (107)

Highlands Oncology Group.

Springdale, Arkansas, 72762, United States

RECRUITING

Kaiser Permanente - Baldwin Park

Baldwin Park, California, 91706, United States

SUSPENDED

City of Hope Cancer Center

Duarte, California, 91010, United States

SUSPENDED

Kaiser Permanente - Los Angeles (N. Vermont)

Los Angeles, California, 90027, United States

SUSPENDED

Kaiser Permanente - Riverside

Riverside, California, 92505, United States

SUSPENDED

University of California San Francisco

San Francisco, California, 94158, United States

SUSPENDED

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

MSK Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

MSK Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

MSK Commack

Commack, New York, 11725, United States

RECRUITING

MSK Westchester

Harrison, New York, 10604, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

SUSPENDED

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MSK Nassau

Uniondale, New York, 11553, United States

RECRUITING

Providence Portland Medical Ctr

Portland, Oregon, 97225, United States

SUSPENDED

AHN Cancer Institute ? Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

SUSPENDED

Bon Secours - St. Francis Hospital

Greenville, South Carolina, 29607, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

Instituto Alexander Fleming

Buenos Aires, 1426, Argentina

RECRUITING

Hospital Britanico

Buenos Aires, C1280AEB, Argentina

RECRUITING

Hospital Italiano

Ciudad Autonoma Buenos Aires, C1199ABB, Argentina

RECRUITING

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

RECRUITING

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

RECRUITING

Sunshine Hospital

St Albans, Victoria, 3021, Australia

RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

AZ Groeninge

Kortrijk, 8500, Belgium

RECRUITING

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

Clinique Ste-Elisabeth

Namur, 5000, Belgium

RECRUITING

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-000, Brazil

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

SUSPENDED

Aalborg Universitetshospital

Aalborg, 9000, Denmark

RECRUITING

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

RECRUITING

Herlev Hospital

Herlev, 2730, Denmark

RECRUITING

Hopital Claude Huriez

Lille, 59000, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13273, France

RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

SUSPENDED

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Vivantes Klinikum Am Urban

Berlin, 10967, Germany

SUSPENDED

Universitätsklinikum Düsseldorf;Urologische Klinik

Düsseldorf, 40225, Germany

RECRUITING

Uniklinik Essen

Essen, 45122, Germany

RECRUITING

Uniklinik-Eppendorf

Hamburg, 20246, Germany

SUSPENDED

Uniklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Marien Hospital Herne

Herne, 44625, Germany

RECRUITING

Universitätsklinikum Jena, Urologische Klinik und Poliklinik

Jena, 07747, Germany

RECRUITING

Klinikum rechts der Isar der TU München

München, 81675, Germany

SUSPENDED

Klinikum Stuttgart - Katharinenhospital

Stuttgart, 70174, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

Alexandras Hospital

Athens, 115 28, Greece

SUSPENDED

Attikon University General Hospital

Athens, 124 61, Greece

RECRUITING

Theageneio Hospital

Thessaloniki, 546 39, Greece

RECRUITING

A.O. Universitaria Ospedale Consorziale Policlinico Di Bari

Bari, Apulia, 70124, Italy

RECRUITING

Istituto Nazionale Tumori Irccs Fondazione G. Pascale

Naples, Campania, 80131, Italy

RECRUITING

AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

IFO - Istituto Regina Elena

Rome, Lazio, 00144, Italy

RECRUITING

Asst Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

SUSPENDED

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

SUSPENDED

A.O. Universitaria S. Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

RECRUITING

IOV - Istituto Oncologico Veneto - IRCCS

Padova, Veneto, 35128, Italy

RECRUITING

A.O.U di Verona Policlinico G.B. Rossi

Verona, Veneto, 37134, Italy

RECRUITING

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

SUSPENDED

CUAN Hospital

San Pedro Garza García, Nuevo León, 66278, Mexico

NOT YET RECRUITING

Erasmus MC

Rotterdam, 3015 GD, Netherlands

RECRUITING

St. Antonius locatie Leidsche Rijn

Utrecht, 3543 AZ, Netherlands

SUSPENDED

Akershus universitetssykehus

Lørenskog, 1474, Norway

SUSPENDED

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, 85-796, Poland

RECRUITING

Szpital Wojewodzki im. M. Kopernika w Koszalinie

Koszalin, 75-581, Poland

RECRUITING

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli

Lublin, 20-090, Poland

RECRUITING

Szpital Kliniczny Ministerstwa Spraw Wewn?trznych i Administracji z Warmi?sko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, 10-228, Poland

RECRUITING

Radomskie Centrum Onkologii

Radom, 26-600, Poland

RECRUITING

AIDPORT Sp. z o. o.

Skórzewo, 60-185, Poland

RECRUITING

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie

Warsaw, 02-781, Poland

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07014, Spain

RECRUITING

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

SUSPENDED

Vall d'Hebron Institute of Oncology (VHIO), Barcelona

Sant Andreu de la Barca, Barcelona, 08740, Spain

RECRUITING

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, LA Coruna, 15706, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Instituto Valenciano Oncologia

Valencia, 46009, Spain

RECRUITING

Hospital General Universitario de Valencia

Valencia, 46014, Spain

RECRUITING

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

RECRUITING

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

RECRUITING

Skånes Onkologiska Klinik, Universitetssjukhuset

Lund, 22185, Sweden

RECRUITING

Chang Gung Medical Foundation - Kaohsiung

Kaohsiung City, Taiwan

RECRUITING

National Taiwan Uni Hospital

Taipei, 100, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112, Taiwan

RECRUITING

Clatterbridge Cancer Centre

Bebington, CH63 4JY, United Kingdom

RECRUITING

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

RECRUITING

Barts & London School of Med;Medical Oncology

London, EC1M 6BQ, United Kingdom

SUSPENDED

Royal Preston Hosptial

Preston, PR2 9HT, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Interventions

Nivolumab; Sodium Chloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: BO45230 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 2, 2024
• Study Start: December 9, 2024
• Primary Completion (Estimated): November 10, 2027
• Study Completion (Estimated): November 10, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AR (3); IT (9); US (26); DE (10); GR (3); SE (2); CA (4); NO (1); BR (1); NL (2); GB (5); KR (5); DK (3); TW (3); BE (4); FR (4); AU (3); ES (10); PL (7); ME (2)