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NCT06534983PHASE2Recruiting

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)

Hoffmann-La Roche

Start Date

12/9/2024

Completion Date

11/10/2027

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Autogene Cevumeran

DRUG

Nivolumab

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Conditions

Muscle-invasive Urothelial Carcinoma

Locations

Highlands Oncology Group.

Springdale, Arkansas 72762

United States

Kaiser Permanente - Baldwin Park

Baldwin Park, California 91706

United States

City of Hope Cancer Center

Duarte, California 91010

United States

Kaiser Permanente - Los Angeles (N. Vermont)

Los Angeles, California 90027

United States

Kaiser Permanente - Riverside

Riverside, California 92505

United States

University of California San Francisco

San Francisco, California 94158

United States

Yale Cancer Center

New Haven, Connecticut 06520

United States

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia 20007

United States

Norton Cancer Institute

Louisville, Kentucky 40207

United States

Henry Ford Health System

Detroit, Michigan 48202

United States

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey 07920

United States

MSK Monmouth

Middletown, New Jersey 07748

United States

MSK Bergen

Montvale, New Jersey 07645

United States

MSK Commack

Commack, New York 11725

United States

MSK Westchester

Harrison, New York 10604

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

MSK Nassau

Uniondale, New York 11553

United States

Providence Portland Medical Ctr

Portland, Oregon 97225

United States

AHN Cancer Institute ? Allegheny General Hospital

Pittsburgh, Pennsylvania 15212

United States

Rhode Island Hospital

Providence, Rhode Island 02903

United States

Bon Secours - St. Francis Hospital

Greenville, South Carolina 29607

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Inova Schar Cancer Institute

Fairfax, Virginia 22031

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109

United States

University of Washington Medical Center

Seattle, Washington 98195

United States

Instituto Alexander Fleming

Buenos Aires, 1426

Argentina

Hospital Britanico

Buenos Aires, C1280AEB

Argentina

Hospital Italiano

Ciudad Autonoma Buenos Aires, C1199ABB

Argentina

Lyell McEwin Hospital

Elizabeth Vale, South Australia 5112

Australia

Box Hill Hospital

Box Hill, Victoria 3128

Australia

Sunshine Hospital

St Albans, Victoria 3021

Australia

UZ Gent

Ghent, 9000

Belgium

AZ Groeninge

Kortrijk, 8500

Belgium

UZ Leuven Gasthuisberg

Leuven, 3000

Belgium

Clinique Ste-Elisabeth

Namur, 5000

Belgium

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul 90035-000

Brazil

Cross Cancer Institute

Edmonton, Alberta T6G 1Z2

Canada

Princess Margaret Cancer Center

Toronto, Ontario M5G 1Z5

Canada

Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

McGill University Health Center

Montreal, Quebec H4A 3J1

Canada

Aalborg Universitetshospital

Aalborg, 9000

Denmark

Aarhus Universitetshospital

Aarhus N, 8200

Denmark

Herlev Hospital

Herlev, 2730

Denmark

Hopital Claude Huriez

Lille, 59000

France

Institut Paoli Calmettes

Marseille, 13273

France

Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer

Rennes, 35000

France

Institut Gustave Roussy

Villejuif, 94805

France

Vivantes Klinikum Am Urban

Berlin, 10967

Germany

Universitätsklinikum Düsseldorf;Urologische Klinik

Düsseldorf, 40225

Germany

Uniklinik Essen

Essen, 45122

Germany

Uniklinik-Eppendorf

Hamburg, 20246

Germany

Uniklinikum Heidelberg

Heidelberg, 69120

Germany

Marien Hospital Herne

Herne, 44625

Germany

Universitätsklinikum Jena, Urologische Klinik und Poliklinik

Jena, 07747

Germany

Klinikum rechts der Isar der TU München

München, 81675

Germany

Klinikum Stuttgart - Katharinenhospital

Stuttgart, 70174

Germany

Universitätsklinikum Ulm

Ulm, 89081

Germany

Alexandras Hospital

Athens, 115 28

Greece

Attikon University General Hospital

Athens, 124 61

Greece

Theageneio Hospital

Thessaloniki, 546 39

Greece

A.O. Universitaria Ospedale Consorziale Policlinico Di Bari

Bari, Apulia 70124

Italy

Istituto Nazionale Tumori Irccs Fondazione G. Pascale

Naples, Campania 80131

Italy

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

Bologna, Emilia-Romagna 40138

Italy

IFO - Istituto Regina Elena

Rome, Lazio 00144

Italy

Asst Papa Giovanni XXIII

Bergamo, Lombardy 24127

Italy

Istituto Clinico Humanitas

Rozzano, Lombardy 20089

Italy

A.O. Universitaria S. Luigi Gonzaga

Orbassano, Piedmont 10043

Italy

IOV - Istituto Oncologico Veneto - IRCCS

Padova, Veneto 35128

Italy

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

Verona, Veneto 37134

Italy

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco 44280

Mexico

CUAN Hospital

San Pedro Garza García, Nuevo León 66278

Mexico

Erasmus MC

Rotterdam, 3015 GD

Netherlands

St. Antonius locatie Leidsche Rijn

Utrecht, 3543 AZ

Netherlands

Akershus universitetssykehus

Lørenskog, 1474

Norway

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, 85-796

Poland

Szpital Wojewodzki im. M. Kopernika w Koszalinie

Koszalin, 75-581

Poland

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli

Lublin, 20-090

Poland

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

Olsztyn, 10-228

Poland

Radomskie Centrum Onkologii

Radom, 26-600

Poland

AIDPORT Sp. z o. o.

Skórzewo, 60-185

Poland

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie

Warsaw, 02-781

Poland

Seoul National University Bundang Hospital

Seongnam-si, 463-707

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands 07014

Spain

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona 08908

Spain

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

Sant Andreu de la Barca, Barcelona 08740

Spain

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, LA Coruna 15706

Spain

Hospital Clinico San Carlos

Madrid, 28040

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital Universitario Virgen del Rocio

Seville, 41013

Spain

Instituto Valenciano Oncologia

Valencia, 46009

Spain

Hospital General Universitario de Valencia

Valencia, 46014

Spain

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009

Spain

Sahlgrenska University Hospital

Gothenburg, 413 45

Sweden

Skånes Onkologiska Klinik, Universitetssjukhuset

Lund, 22185

Sweden

Chang Gung Medical Foundation - Kaohsiung

Kaohisung, DUMMY_VALUE

Taiwan

National Taiwan Uni Hospital

Taipei, 100

Taiwan

Taipei Veterans General Hospital

Taipei, 112

Taiwan

Clatterbridge Cancer Centre

Bebington, CH63 4JY

United Kingdom

Royal Devon and Exeter Hospital

Exeter, EX2 5DW

United Kingdom

Barts & London School of Med;Medical Oncology

London, EC1M 6BQ

United Kingdom

Royal Preston Hosptial

Preston, PR2 9HT

United Kingdom

Southampton General Hospital

Southampton, SO16 6YD

United Kingdom