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
- Conditions
- Urothelial Cancer
- Interventions
- Registration Number
- NCT05645692
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 204
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Atezolizumab Participants will receive intravenous (IV) atezolizumab every 3 weeks (Q3W). Arm C Tiragolumab Participants will receive IV tobemstomig + IV tiragolumab Q3W. Arm B Tobemstomig Participants will receive IV tobemstomig Q3W. Arm C Tobemstomig Participants will receive IV tobemstomig + IV tiragolumab Q3W.
- Primary Outcome Measures
Name Time Method Incidence and Severity of Adverse Events Up to approximately 30 months
- Secondary Outcome Measures
Name Time Method 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 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 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
Related Research Topics
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Trial Locations
- Locations (61)
Aarhus Universitetshospital
🇩🇰Aarhus N, Denmark
Royal Marsden Hospital
🇬🇧London, United Kingdom
Royal Preston Hosptial
🇬🇧Preston, United Kingdom
Lister Hospital
🇬🇧Stevenage, United Kingdom
Royal Marsden Hospital (Sutton)
🇬🇧Sutton, United Kingdom
Hospital de Amor Amazônia
🇧🇷Porto Velho, Rondônia, Brazil
Szpital Wojewódzki im. Miko?aja Kopernika
🇵🇱Koszalin, Poland
Szpital Uniwersytecki w Krakowie
🇵🇱Kraków, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Pozna?, Poland
Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
🇵🇱Warszawa, Poland
Vall d'Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Institut Catala d Oncologia Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Universitario Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Adana Baskent University Medical Faculty
🇹🇷Adana, Turkey
Ankara City Hospital
🇹🇷Ankara, Turkey
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
🇹🇷Edirne, Turkey
Izmir Medical Point Hospital
🇹🇷Izmir, Turkey
Goztepe Prof.Dr. Suleyman Yalcin City Hospital
🇹🇷Kadiköy, Turkey
Barts and the London NHS Trust
🇬🇧London, United Kingdom
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Macquarie University Hospital
🇦🇺Macquarie Park, New South Wales, Australia
Lyell McEwin Hospital
🇦🇺Adelaide, South Australia, Australia
ICON Cancer Care Adelaide
🇦🇺Kurralta Park, South Australia, Australia
Hospital Universitario Evangelico De Curitiba
🇧🇷Curitiba, Paraná, Brazil
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
🇧🇷Santo André, São Paulo, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, São Paulo, Brazil
Beijing Cancer Hospital
🇨🇳Beijing, China
West China Hospital - Sichuan University
🇨🇳Chengdu City, China
Sun yat-sen University Cancer Center
🇨🇳Guangzhou, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai City, China
Herlev Hospital
🇩🇰Herlev, Denmark
Odense Universitetshospital, Onkologisk Afdeling, Klinisk Forsknings Enhed
🇩🇰Odense C, Denmark
Centre Leon Berard
🇫🇷Lyon CEDEX 08, France
Gustave Roussy
🇫🇷Villejuif CEDEX, France
Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie
🇩🇪Halle (Saale), Germany
Martini-Klinik am UKE GmbH
🇩🇪Hamburg, Germany
Alexandras General Hospital of Athens
🇬🇷Athens, Greece
Attikon University General Hospital
🇬🇷Chaidari, Greece
Theageneio Hospital
🇬🇷Thessaloniki, Greece
Istituto Nazionale Tumori Irccs Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
🇮🇹Meldola, Emilia-Romagna, Italy
Policlinico Universitario "Agostino Gemelli"
🇮🇹Roma, Lazio, Italy
Irccs Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
🇮🇹Bari, Puglia, Italy
Azienda Ospedaliera S. Maria - Terni
🇮🇹Terni, Umbria, Italy
IRCCS Istituto Oncologico Veneto (IOV)
🇮🇹Padova, Veneto, Italy
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
Centro Medico Nacional Siglo Xxi - Imss
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Instituto Nacional de Cancerologia
🇲🇽Mexico City, Mexico CITY (federal District), Mexico