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

Urothelial Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05645692
• Other study ID #: BO44157
• Status: Recruiting
• Phase: Phase 2
• Start date: April 13, 2023
• Est. completion date: December 30, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO44157 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 30, 2026
• Est. primary completion date: December 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Urothelial Cancer

Intervention

Drug:
• Atezolizumab
Participants will receive 1200 mg IV atezolizumab Q3W.
• Tobemstomig
Participants will receive 600 mg IV tobemstomig Q3W.
• Tiragolumab
Participants will receive 600 mg IV tiragolumab Q3W.

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Adelaide	South Australia
Australia	ICON Cancer Care Adelaide	Kurralta Park	South Australia
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Brazil	Hospital Universitario Evangelico De Curitiba	Curitiba	PR
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital de Amor Amazônia	Porto Velho	RO
Brazil	Oncoclinicas Rio de Janeiro S.A.	Rio de Janeiro	RJ
Brazil	*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo André	SP
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo	SP
China	Beijing Cancer Hospital	Beijing
China	Peking University First Hospital	Beijing City
China	West China Hospital - Sichuan University	Chengdu City
China	Sun yat-sen University Cancer Center; Internal Medicine of Oncology	Guangzhou
China	Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai City
China	Tianjin Cancer Hospital; urologic tumor	Tianjin City
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
Denmark	Aalborg Universitetshospital; Onkologisk Afdeling	Aalborg
Denmark	Aarhus Universitetshospital; Kræftafdelingen	Aarhus N
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Odense Universitetshospital, Onkologisk Afdeling, Klinisk Forsknings Enhed	Odense C
France	CHRU Besançon	Besançon
France	CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre	Bordeaux
France	Centre Leon Berard	Lyon CEDEX 08
France	Institut Régional du Cancer de Montpellier	Montpellier
France	Centre Eugène Marquis	Rennes
France	Gustave Roussy	Villejuif
Germany	Universitätsklinikum Düsseldorf; Urologische Klinik	Düsseldorf
Germany	Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie	Halle (Saale)
Germany	Martini-Klinik am UKE GmbH	Hamburg
Germany	Universitaetsklinikum Muenster; Urology	Muenster
Germany	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	Athens Medical Center; Dept. of Oncology	Athens
Greece	Attikon University General Hospital	Chaidari
Greece	Theageneio Hospital	Thessaloniki
Italy	A.O. Universitaria Ospedale Consorziale Policlinico Di Bari; U.O. Oncologia Medica Universitaria	Bari	Puglia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Irccs Ospedale San Raffaele	Milano	Lombardia
Italy	ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico	Napoli	Campania
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica	Roma	Lazio
Italy	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria
Korea, Republic of	Seoul National University Bundang Hospital; Internal Medicine	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Centro Medico Nacional Siglo Xxi - Imss; Hospital de Oncologia	Mexico City	Mexico CITY (federal District)
Mexico	Instituto Nacional de Cancerologia	Mexico City	Mexico CITY (federal District)
Poland	Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii	Koszalin
Poland	Szpital Uniwersytecki w Krakowie; Oddzial Kliniczny Onkologii i Poradnia Onkologiczna	Kraków
Poland	ZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii;Wojska Polskiego 37	Olsztyn
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.	Warszawa
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Turkey	Adana Baskent University Medical Faculty; Oncology	Adana
Turkey	Ankara City Hospital; Oncology	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; Clinical Oncology	Kadiköy
United Kingdom	Western General Hospital; Clinical Oncology	Edinburgh
United Kingdom	Barts and the London NHS Trust	London
United Kingdom	Royal Preston Hosptial	Preston
United Kingdom	Lister Hospital; Oncology Dept	Stevenage
United Kingdom	Royal Marsden Hospital (Sutton)	Sutton
United States	Sarah Cannon Research Institute / Tennessee Oncology	Chattanooga	Tennessee
United States	Cleveland Clinic	Cleveland	Ohio
United States	SCRI Mark H. Zangmeister Center	Columbus	Ohio
United States	MD Anderson Cancer Center; Oncology	Houston	Texas
United States	Sarah Cannon Research Institute / Tennessee Oncology	Nashville	Tennessee
United States	Advent Health Orlando	Orlando	Florida
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  Denmark,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Mexico,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

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