Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)
- Conditions
- Urothelial CarcinomaBladder Cancer
- Interventions
- Registration Number
- NCT03869190
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 272
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 1) Enfortumab Vedotin Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Niraparib for mUC Cohort (Stage 1) Niraparib Participants will receive atezolizumab and Niraparib (Nira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Magrolimab for mUC Cohort (Stage 1) Magrolimab (Hu5F9-G4) Participants will receive atezolizumab and magrolimab (Hu5F9-G4) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 2 Tiragolumab Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery. Atezolizumab + Niraparib for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and Niraparib (Nira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Magrolimab for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and magrolimab (Hu5F9-G4) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Tiragolumab for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and Tiragolumab (Tira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Tiragolumab for mUC Cohort (Stage 1) Tiragolumab Participants will receive atezolizumab and Tiragolumab (Tira) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and Sacituzumab Govitecan (SG) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 1) Sacituzumab Govitecan Participants will receive atezolizumab and Sacituzumab Govitecan (SG) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Tocilizumab for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and Tocilizumab (TCZ) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Tocilizumab for mUC Cohort (Stage 1) Tocilizumab Participants will receive atezolizumab and Tocilizumab (TCZ) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 2) Enfortumab Vedotin Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 2) Atezolizumab Participants will receive atezolizumab and Sacituzumab Govitecan (SG) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + RO7122290 for mUC Cohort (Stage 1) Atezolizumab Participants will receive atezolizumab and RO7122290 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 2) Atezolizumab Participants will receive atezolizumab and Enfortumab Vedotin (EV) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 2) Sacituzumab Govitecan Participants will receive atezolizumab and Sacituzumab Govitecan (SG) until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status. Enrollment is closed. Atezolizumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 1 Atezolizumab Participants will receive Atezolizumab for 3 cycles pre-surgery and 14 cycles post-surgery. Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 2 Atezolizumab Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery. Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 2 Atezolizumab Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 1 Cisplatin Participants will receive 3 cycles of Atezolizumab, Cisplatin, and Gemcitabine pre-surgery and 14 cycles of Atezolizumab only post-surgery. Atezolizumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 1 Atezolizumab Participants will receive Atezolizumab for 3 cycles pre-surgery and 14 cycles post-surgery. Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 2 Tiragolumab Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 1 Atezolizumab Participants will receive 3 cycles of Atezolizumab, Cisplatin, and Gemcitabine pre-surgery and 14 cycles of Atezolizumab only post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 1 Gemcitabine Participants will receive 3 cycles of Atezolizumab, Cisplatin, and Gemcitabine pre-surgery and 14 cycles of Atezolizumab only post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 2 Atezolizumab Participants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 2 Tiragolumab Participants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 2 Cisplatin Participants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery. Cisplatin-eligible MIBC Cohort 3 Arm 2 Gemcitabine Participants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery.
- Primary Outcome Measures
Name Time Method pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts Randomization to approximately 5-7 years pCR, defined as the proportion of participants with an absence of residual invasive cancer of the complete resected specimen.
Objective Response Rate (ORR) for mUC Cohort Stage 1 Baseline until disease progression or loss of clinical benefit (approximately 5-7 years) 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.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) for mUC Cohort Stage 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 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.
Overall Survival (OS) for mUC Cohort Stage 1 Randomization to death from any cause, through the end of study (approximately 5-7 years) OS after randomization,defined as the time from randomization to death from any cause.
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 Percentage of Participants with Adverse Events for MIBC Cohorts Baseline to approximately 5-7 years Overall Survival (at specific time-points) for mUC Cohort Stage 1 12 months OS rate at specific timepoints, defined as the proportion of patients who have not experienced death from any cause at that timepoint.
Duration of Response (DOR) for mUC Cohort Stage 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) 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.
Disease Control Rate (DCR) for mUC Cohort Stage 1 Baseline through end of study (approximately 5-7 years) Disease control, defined as stable disease \>= 18 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1.
Presence of ADAs to Atezolizumab for mUC Cohort Stage 2 Baseline to approximately 5-7 years For drugs for which ADA formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline.
Landmark Recurrence-Free Survival (RFS) for MIBC Cohorts 12, 18, 24 months Landmark RFS, defined as RFS at specific timepoints.
Percentage of Participants with Adverse Events for mUC Cohort Stage 1 Baseline to end of study (approximately 5-7 years) 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 Percentage of Participants with Adverse Events for mUC Cohort Stage 2 Baseline to end of study (approximately 5-7 years) Landmark Event-Free Survival (EFS) for MIBC Cohorts 12, 18, 24 months Landmark EFS, defined as EFS at specific timepoints.
Landmark Overall Survival (OS) for MIBC Cohorts 12, 18, 24 months Landmark OS, defined as OS at specific timepoints.
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
Trial Locations
- Locations (34)
Stanford Cancer Center
🇺🇸Stanford, California, United States
Institut Claudius Regaud
🇫🇷Toulouse, France
UCLA Department of Medicine
🇺🇸Los Angeles, California, United States
UCSF Comprehensive Cancer Ctr
🇺🇸San Francisco, California, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸Commack, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Centre Francois Baclesse
🇫🇷Caen, France
Centre Leon Berard
🇫🇷Lyon, France
Institut régional du Cancer Montpellier
🇫🇷Montpellier, France
Attiko Hospital University of Athens
🇬🇷Athens, Greece
Athens Medical Center
🇬🇷Athens, Greece
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
🇪🇸L?Hospitalet De Llobregat, Barcelona, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
🇪🇸Santiago de Compostela, LA Coruna, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital General Universitario Gregorio Mara
🇪🇸Madrid, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz.
🇪🇸Madrid, Spain
Hospital Univ 12 de Octubre
🇪🇸Madrid, Spain
START Madrid. Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Barts and The London
🇬🇧London, United Kingdom
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom