A Study Evaluating Different Immunotherapies (LAG-3 and PD-1 With or Without TIGIT, Compared to PD-L1 Alone) in Participants With Untreated Locally Advanced Metastatic Urothelial Cancer

NCT05645692 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: BO44157
• Study Type: interventional
• Target: 204
• Locations: 15 countries
• Sites: 56

Brief Summary

This study will evaluate the safety of tobemstomig alone or in combination with tiragolumab compared with atezolizumab in participants with previously untreated, locally advanced or metastatic urothelial cancer (mUC) who are ineligible to receive a platinum containing chemotherapy.

Conditions

Urothelial Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Adverse Events

  Up to approximately 30 months

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Participants will receive intravenous (IV) atezolizumab every 3 weeks (Q3W).

Drug: Atezolizumab

Arm B

EXPERIMENTAL

Participants will receive IV tobemstomig Q3W.

Drug: Tobemstomig

Arm C

EXPERIMENTAL

Participants will receive IV tobemstomig + IV tiragolumab Q3W.

Drug: Tobemstomig; Drug: Tiragolumab

Interventions

Atezolizumab DRUG

Participants will receive 1200 mg IV atezolizumab Q3W.

Arm A

Tobemstomig DRUG

Participants will receive 600 mg IV tobemstomig Q3W.

Also known as: RO7247669

Arm B; Arm C

Tiragolumab DRUG

Participants will receive 600 mg IV tiragolumab Q3W.

Arm C

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Ineligible ("unfit") to receive platinum-based chemotherapy
• No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma (UC)
• Measurable disease; at least one measurable lesion as defined by response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)
• Availability of a representative leftover tumor specimen that is suitable for determination of PD-L1 status as assessed by a central laboratory
• Adequate hematologic and end organ function
• Negative for hepatitis B and hepatitis C virus (HCV)
• Adequate cardiovascular function

You may not qualify if:

• Pregnancy or breastfeeding
• GFR \<15 mL/min/1.73 m2
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• History of leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled or symptomatic hypercalcemia
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Active tuberculosis (TB) or acute Epstein-Barr virus (EBV)
• Significant cardiovascular/cerebrovascular disease within 3 months prior to initiation of study treatment
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• History of another primary malignancy other than urothelial carcinoma within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease \[COPD\] exacerbation), or who are receiving oral antibiotics to treat a urinary tract infection are eligible for the study

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (56)

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2113, Australia

Location

Lyell McEwin Hospital

Adelaide, South Australia, 5112, Australia

Location

ICON Cancer Care Adelaide

Kurralta Park, South Australia, 5037, Australia

Location

Hospital Universitario Evangelico De Curitiba

Curitiba, Paraná, 80440-220, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital de Amor Amazônia

Porto Velho, Rondônia, 76834-899, Brazil

Location

*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia

Santo André, São Paulo, 09060-650, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, São Paulo, 01323-903, Brazil

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

West China Hospital - Sichuan University

Chengdu, 610047, China

Location

Sun yat-sen University Cancer Center

Guangzhou, 510060, China

Location

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200025, China

Location

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Centre Leon Berard

Lyon, 69373, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie

Halle, 06120, Germany

Location

Martini-Klinik am UKE GmbH

Hamburg, 20246, Germany

Location

Alexandras General Hospital of Athens

Athens, 115 28, Greece

Location

Attikon University General Hospital

Chaïdári, 124 62, Greece

Location

Theageneio Hospital

Thessaloniki, 54007, Greece

Location

A.O. Universitaria Ospedale Consorziale Policlinico Di Bari

Bari, Apulia, 70124, Italy

Location

Istituto Nazionale Tumori Irccs Fondazione G. Pascale

Naples, Campania, 80131, Italy

Location

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna, 47014, Italy

Location

Policlinico Universitario "Agostino Gemelli"

Rome, Lazio, 00168, Italy

Location

Irccs Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Azienda Ospedaliera S. Maria - Terni

Terni, Umbria, 05100, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV)

Padova, Veneto, 35128, Italy

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Szpital Wojewódzki im. Miko?aja Kopernika

Koszalin, 75-581, Poland

Location

Szpital Uniwersytecki w Krakowie

Krakow, 31-501, Poland

Location

Pratia Poznan

Późna, 60-192, Poland

Location

Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.

Warsaw, 04-073, Poland

Location

Seoul National University Bundang Hospital

Gyeonggi-do, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Barcelona, 08035, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Universitario Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Adana Baskent University Medical Faculty

Adana, 01220, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi

Edirne, 22030, Turkey (Türkiye)

Location

Izmir Medical Point Hospital

Izmir, 35101, Turkey (Türkiye)

Location

Goztepe Prof.Dr. Suleyman Yalcin City Hospital

Kadiköy, 34722, Turkey (Türkiye)

Location

Barts and the London NHS Trust

London, E1 2ES, United Kingdom

Location

Royal Preston Hosptial

Preston, PR2 9HT, United Kingdom

Location

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Interventions

atezolizumab; Tiragolumab

Study Officials

• Clinical Trials

  Hoffmann-LaRoche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: December 9, 2022
• Study Start: April 13, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); ME (1); TU (5); DK (2); GB (3); IT (8); PL (4); FR (2); KR (6); US (2); ES (6); GR (3); CN (4); AU (3); BR (5)