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 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: BO452302023-509023-40-00
• Study Type: interventional
• Target: 62
• Locations: 15 countries
• Sites: 43

Brief 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.

Conditions

Muscle-invasive Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs)

  Up to approximately 15 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

Nivolumab

ACTIVE COMPARATOR

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

Drug: Nivolumab

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; 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 (43)

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

MSK Monmouth

Middletown, New Jersey, 07748, United States

Location

MSK Bergen

Montvale, New Jersey, 07645, United States

Location

MSK Commack

Commack, New York, 11725, United States

Location

MSK Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MSK Nassau

Uniondale, New York, 11553, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Hospital Italiano

Ciudad Autonoma Buenos Aires, C1199ABB, Argentina

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

Location

Aalborg Universitetshospital

Aalborg, 9000, Denmark

Location

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Vivantes Klinikum Am Urban

Berlin, 10967, Germany

Location

Uniklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Marien Hospital Herne

Herne, 44625, Germany

Location

Klinikum Stuttgart - Katharinenhospital

Stuttgart, 70174, Germany

Location

Attikon University General Hospital

Athens, 124 61, Greece

Location

Theageneio Hospital

Thessaloniki, 546 39, Greece

Location

A.O. Universitaria Ospedale Consorziale Policlinico Di Bari

Bari, Apulia, 70124, Italy

Location

IFO - Istituto Regina Elena

Rome, Lazio, 00144, Italy

Location

A.O. Universitaria S. Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

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

Verona, Veneto, 37134, Italy

Location

Akershus universitetssykehus

Lørenskog, 1474, Norway

Location

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, 85-796, Poland

Location

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

Olsztyn, 10-228, Poland

Location

AIDPORT Sp. z o. o.

Skórzewo, 60-185, Poland

Location

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

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

Sant Andreu de la Barca, Barcelona, 08740, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Chang Gung Medical Foundation - Kaohsiung

Kaohisung, DUMMY_VALUE, Taiwan

Location

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

Barts & London School of Med;Medical Oncology

London, EC1M 6BQ, United Kingdom

Location

Related Links

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MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

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: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

NO (1); GR (2); US (9); PL (3); DK (3); AU (1); CA (2); AR (1); DE (4); ES (5); TW (1); GB (2); SE (1); KR (4); IT (4)