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

A Phase II, Randomized, Multicenter, Open-Label, Controlled Study of Tobemstomig Alone or in Combination With Tiragolumab Versus Atezolizumab in Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer Who Are Ineligible for Platinum-Containing Chemotherapy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Urothelial Cancer
• Intervention / Treatment: Drug: Atezolizumab; Drug: Tiragolumab; Drug: Tobemstomig

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2113
      • Macquarie University Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5112
      • Lyell McEwin Hospital
    • Kurralta Park, South Australia, Australia, 5037
      • ICON Cancer Care Adelaide
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80440-220
      • Hospital Universitario Evangelico De Curitiba
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • Rondônia
    • Porto Velho, Rondônia, Brazil, 76834-899
      • Hospital de Amor Amazônia
  • São Paulo
    • Santo André, São Paulo, Brazil, 09060-650
      • *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
    • São Paulo, São Paulo, Brazil, 01323-903
      • Hospital Alemao Oswaldo Cruz
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Chengdu, China, 610047
    • West China Hospital - Sichuan University
  • Guangzhou, China, 510060
    • Sun yat-sen University Cancer Center
  • Shanghai, China, 200025
    • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital
  • Herlev, Denmark, 2730
    • Herlev Hospital
• France
  • Lyon, France, 69373
    • Centre Leon Berard
  • Villejuif, France, 94800
    • Gustave Roussy
• Germany
  • Halle, Germany, 06120
    • Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie
  • Hamburg, Germany, 20246
    • Martini-Klinik am UKE GmbH
• Greece
  • Athens, Greece, 115 28
    • Alexandras General Hospital of Athens
  • Chaïdári, Greece, 124 62
    • Attikon University General Hospital
  • Thessaloniki, Greece, 54007
    • Theageneio Hospital
• Italy
  • Apulia
    • Bari, Apulia, Italy, 70124
      • A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
  • Campania
    • Naples, Campania, Italy, 80131
      • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero-Universitaria S.Orsola-Malpighi
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario "Agostino Gemelli"
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • IRCCS Ospedale San Raffaele
  • Umbria
    • Terni, Umbria, Italy, 05100
      • Azienda Ospedaliera S. Maria - Terni
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IRCCS Istituto Oncologico Veneto (IOV)
• Mexico
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
• Poland
  • Koszalin, Poland, 75-581
    • Szpital Wojewódzki im. Miko?aja Kopernika
  • Krakow, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie
  • Późna, Poland, 60-192
    • Pratia Poznań
  • Warsaw, Poland, 04-073
    • Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
• South Korea
  • Gyeonggi-do, South Korea
    • Seoul National University Bundang Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos
  • Madrid, Spain, 28050
    • Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01220
    • Adana Baskent University Medical Faculty
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Izmir, Turkey (Türkiye), 35101
    • Izmir Medical Point Hospital
  • Kadiköy, Turkey (Türkiye), 34722
    • Goztepe Prof.Dr. Suleyman Yalcin City Hospital
• United Kingdom
  • London, United Kingdom, E1 2ES
    • Barts and The London NHS Trust
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hosptial
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital (Sutton)
• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Participants with squamous, sarcomatoid, micropapillary, and glandular variant histologies are eligible for inclusion in the study, provided that a urothelial component is present in the tumor specimen. Participants with other variant histologies or pure variant histologies are not eligible for inclusion in this study
• 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

Exclusion Criteria:

• 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
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment or within 5 months after the final dose of atezolizumab, 4 months after the final dose of tobemstomig, or 90 days after the final dose of tiragolumab
• Current treatment with anti-viral therapy for HBV
• Treatment with any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
• Treatment with investigational therapy within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-TIGIT and anti-LAG3 therapeutic antibodies or pathways targeting agents
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Participants will receive intravenous (IV) atezolizumab every 3 weeks (Q3W).	Drug: Atezolizumab; Participants will receive 1200 mg IV atezolizumab Q3W.
Experimental: Arm B; Participants will receive IV tobemstomig Q3W.	Drug: Tobemstomig; Participants will receive 600 mg IV tobemstomig Q3W.; Other Names: RO7247669
Experimental: Arm C; Participants will receive IV tobemstomig + IV tiragolumab Q3W.	Drug: Tiragolumab; Participants will receive 600 mg IV tiragolumab Q3W.; Drug: Tobemstomig; Participants will receive 600 mg IV tobemstomig Q3W.; Other Names: RO7247669

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and Severity of Adverse Events	Up to approximately 30 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS)	Up to approximately 30 months
Overall Survival (OS)	Up to approximately 30 months
Duration of Response (DOR)	Up to approximately 30 months
PFS	6 months and 12 months
OS	6 months, 12 months, and 18 months
Disease Control Rate (DCR)	Up to 12 weeks
Time to Confirmed Deterioration (TTCD)	Baseline up to 3 weeks
Change from Baseline in European Organisation for Research and Cancer Treatment Item Library 187 (EORTC IL 187) Scores	Up to approximately 30 months
Maximum serum concentration (Cmax) of tiragolumab	Up to approximately 30 months
Minimum serum concentration (Cmin) of tiragolumab	Up to approximately 30 months
Cmax of atezolizumab	Up to approximately 30 months
Cmin of atezolizumab	Up to approximately 30 months
Incidence of Anti-Drug Antibodies (ADAs)	Up to approximately 30 months
Maximum Concentration (Cmax) of Tobemstomig	Up to approximately 30 months
Time of Maximum Concentration (Tmax) of Tobemstomig	Up to approximately 30 months
Clearance (CL) of Tobemstomig	Up to approximately 30 months
Volume of Distribution at Steady State (Vss) of Tobemstomig	Up to approximately 30 months
Area Under the Curve (AUC) of Tobemstomig	Up to approximately 30 months
Half-Life (T1/2) of Tobemstomig	Up to approximately 30 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-LaRoche

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; atezolizumab; Tiragolumab
• Other Study ID Numbers: BO44157

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