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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03869190
Other study ID # WO39613
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date June 1, 2019
Est. completion date November 27, 2027

Study information

Verified date May 2024
Source Hoffmann-La Roche
Contact Reference Study ID Number: WO39613 https://forpatients.roche.com
Phone 888-662-6728 (U.S. Only)
Email global-roche-genentech-trials@gene.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with MIBC and in participants with locally advanced or metastatic Urothelial Carcinoma (UC) who have progressed during or following a platinum-containing regimen. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population (e.g., with regard to prior anti-cancer treatment or biomarker status). Participants in the mUC Cohort who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen for Stage 2.


Recruitment information / eligibility

Status Recruiting
Enrollment 645
Est. completion date November 27, 2027
Est. primary completion date December 6, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria for mUC Cohort: - Histologically documented, locally advanced or metastatic UC (also termed TCC or urothelial cell carcinoma of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra) - Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing - Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence - ECOG Performance Status of 0 or 1 - Measurable disease (at least one target lesion) according to RECIST v1.1 - Adequate hematologic and end-organ function - Negative HIV test at screening - Negative total hepatitis B core antibody (HBcAb) test and hepatitis C virus (HCV) antibody at screening - Tumor accessible for biopsy - For women of childbearing potential: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating eggs - For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm Inclusion Criteria for MIBC Cohorts: - ECOG PS of 0 or 1 - Fit and planned-for cystectomy - Histologically documented MIBC (pT2-4, N0, M0), also termed TCC or urothelial cell carcinoma of the urinary bladder - N0 or M0 disease by CT or MRI - Adequate hematologic and end-organ function - Availability of TURBT specimen - Negative HIV, HBcAb, and HCV test at screening - For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Exclusion Criteria for mUC Cohort: - Prior treatment with a T-cell co-stimulating therapy or a CPI including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies - Prior treatment with any of the protocol-specified study treatments including treatment with poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, nectin-4 targeting agents, signal regulatory protein alpha-targeting agents, or TIGIT-targeting agents, Trop-2 targeting agents, FAP-directed therapies, 4-1BB (CD137)-directed therapies, or topoisomerase 1 inhibitors - Treatment with investigational therapy within 28 days prior to initiation of study treatment - Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment - Eligibility only for the control arm - Prior allogeneic stem cell or solid organ transplantation - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment - Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment - Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Uncontrolled tumor-related pain - Uncontrolled or symptomatic hypercalcemia - Symptomatic, untreated, or actively progressing CNS metastases - History of leptomeningeal disease - 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 - History of malignancy other than UC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death - Active tuberculosis - Severe infection within 4 weeks prior to initiation of study treatment - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment - Significant cardiovascular disease - Uncontrolled hypertension - Grade 3 or greater hemorrhage or bleeding event within 28 days prior to initiation of study treatment - Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment - Pregnancy or breastfeeding, or intention of becoming pregnant during the study - Additional drug-specific exclusion criteria might apply Exclusion for MIBC Cohorts: - Prior treatment with systemic immunostimulatory agents prior to the initiation of study treatment - Eligibility only for the control arm - Prior allogeneic stem cell or solid organ transplantation - Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions: Patients who received acute, low-dose, systemic immunosuppressant medications, or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor approval has been obtained. Patients who received mineralocorticoids, corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. - Severe infection within 4 weeks prior to initiation of study treatment - Pregnancy or breastfeeding, or intention of becoming pregnant during the study - Also includes all the mUC exclusion criteria Additional Exclusion Criteria for Atezo+Tira and Atezo (Atezolizumab) +Tira+Cis (Cisplatin)+Gem (Gemcitabine) in the MIBC Cohorts: - Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening. Additional Exclusion Criteria for the Cisplatin-Eligible MIBC Cohort: - Patients who decline neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate. - Impaired renal function.

Study Design


Intervention

Drug:
Atezolizumab
For the control, + EV, + Nira, + Tira, and + SG arms, + RO7122290, Atezolizumab will be administered intravenously (IV) at a fixed dose of 1200 mg every 3 weeks (Q3W) on Day 1 of each 21-day cycle. For the Atezo + Hu5F9-G4 and + TCZ arms, Atezo will be administered IV at a fixed dose of 840 mg every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle.
Enfortumab Vedotin
Enfortumab vedotin will be administered at a dose of 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle.
Niraparib
Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.
Magrolimab (Hu5F9-G4)
Participants will receive an 1-mg/kg priming dose IV on Day 1 followed by three weekly IV doses of 30 mg/kg on Days 8, 15, and 22. During Cycle 2, participants will receive weekly IV doses of 30 mg/kg on Days 1, 8, 15, and 22. For all subsequent cycles, participants will receive 30 mg/kg on Days 1 and 15. Cycle = 28 days.
Tiragolumab
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
Sacituzumab Govitecan
Sacituzumab Govitecan will be administered at a dose of 10 mg/kg by IV on Day 1 and 8 of each 21-day cycle.
Tocilizumab
Tocilizumab will be administered by IV infusion at a dose of 8 mg/kg every 4 weeks (Q4W) on Day 1 of each 28-day cycle.
Cisplatin
Cisplatin will be administered at a dose of 70mg/m^2 by IV on Day 1 of each cycle for Cycles 1-3 pre-surgery.
Gemcitabine
Gemcitabine will be administered at a dose of 1000mg/m^2 by IV on Days 1 and 8 of each cycle for Cycles 1-3 pre-surgery.

Locations

Country Name City State
France Centre Francois Baclesse; Pharmacie Caen
France Centre Leon Berard Lyon
France Institut régional du Cancer Montpellier Montpellier
France Institut Claudius Regaud; Radiotherapie Toulouse
France Gustave Roussy Cancer Campus Villejuif
Greece Alexandras General Hospital of Athens; Oncology Department Athens
Greece Athens Medical Center; Dept. of Oncology Athens
Greece Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine Athens
Greece University Hospital of Patras Medical Oncology Patras
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine Seoul
Spain Hospital Clinic i Provincial; Servicio de Neurologia Barcelona
Spain Hospital del Mar Barcelona
Spain Vall d?Hebron Institute of Oncology (VHIO), Barcelona Barcelona
Spain Hospital Universitario Reina Sofia Cordoba
Spain ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO L?Hospitalet De Llobregat Barcelona
Spain Hospital General Universitario Gregorio Mara Madrid
Spain Hospital Univ 12 de Octubre Madrid
Spain Hospital Universitario Fundacion Jimenez Diaz. Madrid
Spain MD Anderson Cancer Center Madrid
Spain START Madrid. Centro Integral Oncologico Clara Campal; CIOCC Madrid
Spain Clinica Universitaria de Navarra Pamplona Navarra
Spain Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas Santiago de Compostela LA Coruña
Spain Hospital Clinico Universitario de Valencia Valencia
Taiwan National Taiwan University Hospital, Yun-Lin Branch Huwei Township
Taiwan Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung City
Taiwan National Cheng Kung University Hospital Tainan
Taiwan Taipei Veterans General Hospital Taipei City
United Kingdom Barts and The London London
United Kingdom The Christie NHS Foundation Trust Manchester
United Kingdom Churchill Hospital; Pharmacy Clinical Trials Office, Pharmacy Department Oxford
United Kingdom Royal Marsden NHS Foundation Trust Sutton
United States Levine Cancer Institute Charlotte North Carolina
United States Cleveland Clinic Cleveland Ohio
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States Memorial Sloan-Kettering Cancer Center Commack New York
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States University of Kentucky Chandler Medical Center Lexington Kentucky
United States UCLA Department of Medicine Los Angeles California
United States Norton Cancer Institute Louisville Kentucky
United States Stanford Cancer Center Palo Alto California
United States UCSF Comprehensive Cancer Ctr San Francisco California

Sponsors (2)

Lead Sponsor Collaborator
Hoffmann-La Roche Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas

Countries where clinical trial is conducted

United States,  France,  Greece,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective Response Rate (ORR) for mUC Cohort Stage 1 Objective response rate, defined as the proportion of participants with a CR or PR on two consecutive occasions >=4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1. Baseline until disease progression or loss of clinical benefit (approximately 5-7 years)
Primary pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts pCR, defined as the proportion of participants with an absence of residual invasive cancer of the complete resected specimen. Randomization to approximately 5-7 years
Secondary Progression Free Survival (PFS) for mUC Cohort Stage 1 PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1. Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 5-7 years) as determined by the investigator according to RECIST 1.1
Secondary Overall Survival (OS) for mUC Cohort Stage 1 OS after randomization,defined as the time from randomization to death from any cause. Randomization to death from any cause, through the end of study (approximately 5-7 years)
Secondary Overall Survival (at specific time-points) for mUC Cohort Stage 1 OS rate at specific timepoints, defined as the proportion of patients who have not experienced death from any cause at that timepoint. 12 months
Secondary Duration of Response (DOR) for mUC Cohort Stage 1 DOR, defined as the time from the first occurrence of a documented objective response during Stage 1 to disease progression or death from anycause (whichever occurs first), as determined by the investigator according to RECIST v1.1. Randomization until first occurrence of a documented objective response to the first recorded occurrence of disease progression or death from any cause (whichever occurs first), through end of study (approximately 5-7 years)
Secondary Disease Control Rate (DCR) for mUC Cohort Stage 1 Disease control, defined as stable disease >= 18 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. Baseline through end of study (approximately 5-7 years)
Secondary Percentage of Participants with Adverse Events for mUC Cohort Stage 1 Baseline to end of study (approximately 5-7 years)
Secondary Serum Concentration of Atezolizumab for mUC Cohort Stage 2 At pre-defined intervals from first administration of study drug up to approximately 5-7 years
Secondary Serum Concentration of Enfortumab Vedotin for mUC Cohort Stage 2 At pre-defined intervals from first administration of study drug up to approximately 5-7 years
Secondary Serum Concentration of Sacituzumab Govitecan for mUC Cohort Stage 2 At pre-defined intervals from first administration of study drug up to approximately 5-7 years
Secondary Presence of ADAs to Atezolizumab for mUC Cohort Stage 2 For drugs for which ADA formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline. Baseline to approximately 5-7 years
Secondary Percentage of Participants with Adverse Events for mUC Cohort Stage 2 Baseline to end of study (approximately 5-7 years)
Secondary Landmark Recurrence-Free Survival (RFS) for MIBC Cohorts Landmark RFS, defined as RFS at specific timepoints. 12, 18, 24 months
Secondary Landmark Event-Free Survival (EFS) for MIBC Cohorts Landmark EFS, defined as EFS at specific timepoints. 12, 18, 24 months
Secondary Landmark Overall Survival (OS) for MIBC Cohorts Landmark OS, defined as OS at specific timepoints. 12, 18, 24 months
Secondary Percentage of Participants with Adverse Events for MIBC Cohorts Baseline to approximately 5-7 years
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