Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)
1 other identifier
interventional
272
7 countries
33
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2019
Longer than P75 for phase_1
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 8, 2019
CompletedFirst Posted
Study publicly available on registry
March 11, 2019
CompletedStudy Start
First participant enrolled
June 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 8, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 22, 2025
CompletedJanuary 22, 2026
January 1, 2026
6.4 years
March 8, 2019
January 21, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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)
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 Outcomes (15)
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
Overall Survival (OS) for mUC Cohort Stage 1
Randomization to death from any cause, through the end of study (approximately 5-7 years)
Overall Survival (at specific time-points) for mUC Cohort Stage 1
12 months
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)
Disease Control Rate (DCR) for mUC Cohort Stage 1
Baseline through end of study (approximately 5-7 years)
- +10 more secondary outcomes
Study Arms (16)
Atezolizumab for mUC Cohort (Stage 1)
ACTIVE COMPARATORParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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 + RO7122290 for mUC Cohort (Stage 1)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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)
EXPERIMENTALParticipants 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
ACTIVE COMPARATORParticipants 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
EXPERIMENTALParticipants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery.
Atezolizumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 1
ACTIVE COMPARATORParticipants 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
EXPERIMENTALParticipants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery.
Cisplatin-eligible MIBC Cohort 3 Arm 1
ACTIVE COMPARATORParticipants 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
EXPERIMENTALParticipants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery.
Interventions
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 will be administered at a dose of 200 mg once daily (QD) by mouth.
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 will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
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 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 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 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.
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.
Eligibility Criteria
You may qualify if:
- 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
- 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
- +5 more criteria
You may not qualify if:
- 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
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
UCLA Department of Medicine
Los Angeles, California, 90024, United States
UCSF Comprehensive Cancer Ctr
San Francisco, California, 94115, United States
Stanford Cancer Center
Stanford, California, 94305-5820, United States
University of Kentucky Chandler Medical Center
Lexington, Kentucky, 40536, United States
Norton Cancer Institute
Louisville, Kentucky, 40241, United States
Memorial Sloan-Kettering Cancer Center
Commack, New York, 11725, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44016, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009, United States
Centre Francois Baclesse
Caen, 14076, France
Centre Leon Berard
Lyon, 69008, France
Institut régional du Cancer Montpellier
Montpellier, 34298, France
Institut Claudius Regaud
Toulouse, 31052, France
Attiko Hospital University of Athens
Athens, 12462, Greece
Athens Medical Center
Athens, 151 25, Greece
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Severance Hospital
Seoul, 120-749, South Korea
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago de Compostela, LA Coruna, 15706, Spain
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008, Spain
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona, 08035, Spain
Hospital Clinic i Provincial
Barcelona, 08036, Spain
Institut Catala d Oncologia Hospitalet
Barcelona, 08908, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Hospital General Universitario Gregorio Mara
Madrid, 28009, Spain
MD Anderson Cancer Center
Madrid, 28033, Spain
Hospital Universitario Fundacion Jimenez Diaz.
Madrid, 28040, Spain
Hospital Univ 12 de Octubre
Madrid, 28041, Spain
START Madrid. Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT, United Kingdom
Related Publications (1)
Drakaki A, Powles T, Bamias A, Martin-Liberal J, Shin SJ, Friedlander T, Tosi D, Park C, Gomez-Roca C, Joly Lobbedez F, Castellano D, Morales-Barrera R, Moreno-Candilejo I, Flechon A, Yuen K, Rishipathak D, DuPree K, Young F, Michielin F, Shemesh CS, Steinberg EE, Williams P, Lee JL. Atezolizumab plus Magrolimab, Niraparib, or Tocilizumab versus Atezolizumab Monotherapy in Platinum-Refractory Metastatic Urothelial Carcinoma: A Phase Ib/II Open-Label, Multicenter, Randomized Umbrella Study (MORPHEUS Urothelial Carcinoma). Clin Cancer Res. 2023 Nov 1;29(21):4373-4384. doi: 10.1158/1078-0432.CCR-23-0798.
PMID: 37651261DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2019
First Posted
March 11, 2019
Study Start
June 1, 2019
Primary Completion
October 8, 2025
Study Completion
December 22, 2025
Last Updated
January 22, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing