Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)

Conditions

• Bladder Cancer
• Urothelial Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — DRUG
  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 — DRUG
  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 — DRUG
  Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.
• Magrolimab (Hu5F9-G4) — DRUG
  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 — DRUG
  Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
• Sacituzumab Govitecan — DRUG
  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 — DRUG
  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 — DRUG
  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 — DRUG
  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.

Study Details

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.

Key Dates

Start date

Jun 1, 2019

Status verified

Jan 2026

Primary completion

Oct 8, 2025

Completion

Dec 22, 2025

Study Design

Enrollment

272 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.

Primary Outcome Measure

Objective Response Rate (ORR) for mUC Cohort Stage 1 [ Time Frame: Baseline until disease progression or loss of clinical benefit (approximately 5-7 years) ]

Locations (10)

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