Clinical trial NCT05645692: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Urothelial Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-12-09
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and Severity of Adverse Events
timeFrame: Up to approximately 30 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Kurralta Park
country: Australia
facility: ICON Cancer Care Adelaide
state: South Australia
city: Curitiba
country: Brazil
facility: Hospital Universitario Evangelico De Curitiba
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Porto Velho
country: Brazil
facility: Hospital de Amor Amazônia
state: Rondônia
city: Santo André
country: Brazil
facility: *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: São Paulo
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu City
country: China
facility: West China Hospital - Sichuan University
city: Guangzhou
country: China
facility: Sun yat-sen University Cancer Center
city: Shanghai City
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling, Klinisk Forsknings Enhed
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Halle (Saale)
country: Germany
facility: Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie
city: Hamburg
country: Germany
facility: Martini-Klinik am UKE GmbH
city: Athens
country: Greece
facility: Alexandras General Hospital of Athens
city: Chaidari
country: Greece
facility: Attikon University General Hospital
city: Thessaloniki
country: Greece
facility: Theageneio Hospital
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione G. Pascale
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Orsola-Malpighi
state: Emilia-Romagna
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario "Agostino Gemelli"
state: Lazio
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele
state: Lombardia
city: Bari
country: Italy
facility: A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
state: Puglia
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria - Terni
state: Umbria
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Centro Medico Nacional Siglo Xxi - Imss
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia
state: Mexico CITY (federal District)
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Miko?aja Kopernika
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Pozna?
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Warszawa
country: Poland
facility: Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO), Barcelona
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal
city: Adana
country: Turkey
facility: Adana Baskent University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
city: Izmir
country: Turkey
facility: Izmir Medical Point Hospital
city: Kadiköy
country: Turkey
facility: Goztepe Prof.Dr. Suleyman Yalcin City Hospital
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hosptial
city: Stevenage
country: United Kingdom
facility: Lister Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
Study officials:
affiliation: Hoffmann-LaRoche
name: Clinical Trials
role: STUDY_DIRECTOR
References: