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)

Who is this study for? Patients with locally advanced or metastatic urothelial carcinoma who have progressed during or following a platinum-containing regimen
Status: Active_not_recruiting
Location: See all (32) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

• 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

Locations
United States
California
UCLA Department of Medicine
Los Angeles
UCSF Comprehensive Cancer Ctr
San Francisco
Stanford Cancer Center
Stanford
Kentucky
University of Kentucky Chandler Medical Center
Lexington
Norton Cancer Institute
Louisville
North Carolina
Levine Cancer Institute
Charlotte
New York
Memorial Sloan-Kettering Cancer Center
Commack
Ohio
Cleveland Clinic
Cleveland
University Hospitals Cleveland Medical Center
Cleveland
Texas
The University of Texas MD Anderson Cancer Center
Houston
Other Locations
France
Centre Francois Baclesse
Caen
Centre Leon Berard
Lyon
Institut régional du Cancer Montpellier
Montpellier
Institut Claudius Regaud
Toulouse
Greece
Athens Medical Center
Athens
Republic of Korea
Asan Medical Center
Seoul
Seoul National University Hospital
Seoul
Severance Hospital
Seoul
Spain
Hospital Clinic i Provincial
Barcelona
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
Barcelona
Hospital Universitario Reina Sofia
Córdoba
ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
L'hospitalet De Llobregat
Hospital General Universitario Gregorio Mara
Madrid
Hospital Univ 12 de Octubre
Madrid
Hospital Universitario Fundacion Jimenez Diaz.
Madrid
MD Anderson Cancer Center
Madrid
START Madrid. Centro Integral Oncologico Clara Campal
Madrid
Clinica Universitaria de Navarra
Pamplona
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago De Compostela
Hospital Clinico Universitario de Valencia
Valencia
United Kingdom
Barts and The London
London
Royal Marsden NHS Foundation Trust
Sutton
Time Frame
Start Date: 2019-06-01
Completion Date: 2025-12-22
Participants
Target number of participants: 272
Treatments
Active_comparator: Atezolizumab for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Niraparib for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Magrolimab for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Tiragolumab for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Tocilizumab for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + RO7122290 for mUC Cohort (Stage 1)
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.
Experimental: Atezolizumab + Enfortumab Vedotin for mUC Cohort (Stage 2)
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.
Experimental: Atezolizumab + Sacituzumab Govitecan for mUC Cohort (Stage 2)
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.
Active_comparator: Atezolizumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 1
Participants will receive Atezolizumab for 3 cycles pre-surgery and 14 cycles post-surgery.
Experimental: Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 1 PD-L1+ Arm 2
Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery.
Active_comparator: Atezolizumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 1
Participants will receive Atezolizumab for 3 cycles pre-surgery and 14 cycles post-surgery.
Experimental: Atezolizumab + Tiragolumab for Cisplatin-ineligible MIBC Cohort 2 PD-L1- Arm 2
Participants will receive Atezolizumab and Tiragolumab (Tira) for 3 cycles pre-surgery and 14 cycles post-surgery.
Active_comparator: Cisplatin-eligible MIBC Cohort 3 Arm 1
Participants will receive 3 cycles of Atezolizumab, Cisplatin, and Gemcitabine pre-surgery and 14 cycles of Atezolizumab only post-surgery.
Experimental: Cisplatin-eligible MIBC Cohort 3 Arm 2
Participants will receive Atezolizumab, Tiragolumab (Tira), Cisplatin and Gemcitabine for 3 cycles pre-surgery and 14 cycles of Atezolizumab and Tiragolumab (Tira) post-surgery.
Related Therapeutic Areas
Bladder Cancer
Urothelial Cancer
Sponsors
Collaborators: Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas
Leads: Hoffmann-La Roche

This content was sourced from clinicaltrials.gov

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