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

March 1, 2024 updated by: Hoffmann-La Roche

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)

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

645

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Caen, France, 14076
        • Recruiting
        • Centre Francois Baclesse; Pharmacie
      • Lyon, France, 69008
        • Suspended
        • Centre Leon Berard
      • Montpellier, France, 34298
        • Completed
        • Institut régional du Cancer Montpellier
      • Toulouse, France, 31052
        • Completed
        • Institut Claudius Regaud; Radiotherapie
      • Villejuif, France, 94805
        • Completed
        • Gustave Roussy Cancer Campus
      • Athens, Greece, 115 28
        • Completed
        • Alexandras General Hospital of Athens; Oncology Department
      • Athens, Greece, 12462
        • Recruiting
        • Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine
      • Athens, Greece, 151 25
        • Recruiting
        • Athens Medical Center; Dept. of Oncology
      • Patras, Greece, 265 04
        • Withdrawn
        • University Hospital of Patras Medical Oncology
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Asan Medical Center
      • Seoul, Korea, Republic of, 03080
        • Completed
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 120-749
        • Recruiting
        • Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clinic i Provincial; Servicio de Neurologia
      • Barcelona, Spain, 08003
        • Completed
        • Hospital del Mar
      • Barcelona, Spain, 08035
        • Recruiting
        • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
      • Cordoba, Spain, 14008
        • Recruiting
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28050
        • Recruiting
        • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz.
      • Madrid, Spain, 28009
        • Suspended
        • Hospital General Universitario Gregorio Mara
      • Madrid, Spain, 28033
        • Suspended
        • MD Anderson Cancer Center
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Univ 12 de Octubre
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clínico Universitario de Valencia
    • Barcelona
      • L?Hospitalet De Llobregat, Barcelona, Spain, 08908
        • Recruiting
        • ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
    • LA Coruña
      • Santiago de Compostela, LA Coruña, Spain, 15706
        • Recruiting
        • Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Completed
        • Clinica Universitaria de Navarra
      • Huwei Township, Taiwan, 63247
        • Completed
        • National Taiwan University Hospital, Yun-Lin Branch
      • Kaohsiung City, Taiwan, 807
        • Recruiting
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Tainan, Taiwan, 70457
        • Completed
        • National Cheng Kung University Hospital
      • Taipei City, Taiwan, 112
        • Completed
        • Taipei Veterans General Hospital
      • London, United Kingdom, EC1M 6BQ
        • Recruiting
        • Barts and The London
      • Manchester, United Kingdom, M20 4BX
        • Withdrawn
        • The Christie NHS Foundation Trust
      • Oxford, United Kingdom, OX3 7LJ
        • Completed
        • Churchill Hospital; Pharmacy Clinical Trials Office, Pharmacy Department
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden NHS Foundation Trust
    • California
      • Los Angeles, California, United States, 90024
        • Recruiting
        • UCLA Department of Medicine
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Comprehensive Cancer Ctr
      • Stanford, California, United States, 94305-5820
        • Recruiting
        • Stanford Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University Of Kentucky Chandler Medical Center
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Cancer Institute
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Cancer Institute
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
    • Texas
      • Houston, Texas, United States, 77030-4009
        • Recruiting
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

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.

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.

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 will be administered at a dose of 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle.
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.

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.

Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.
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.

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.

Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
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.

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.

Sacituzumab Govitecan will be administered at a dose of 10 mg/kg by IV on Day 1 and 8 of each 21-day cycle.
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.

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.

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.
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.

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.

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.

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 will be administered at a dose of 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle.
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.

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.

Sacituzumab Govitecan will be administered at a dose of 10 mg/kg by IV on Day 1 and 8 of each 21-day cycle.
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.

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.

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.
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.

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.

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.

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.

Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
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.

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.

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.

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.

Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.
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.

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.

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.
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.

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.

Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) for mUC Cohort Stage 1
Time Frame: 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.
Baseline until disease progression or loss of clinical benefit (approximately 5-7 years)
pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts
Time Frame: 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.
Randomization to approximately 5-7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (at specific time-points) for mUC Cohort Stage 1
Time Frame: 12 months
OS rate at specific timepoints, defined as the proportion of patients who have not experienced death from any cause at that timepoint.
12 months
Landmark Recurrence-Free Survival (RFS) for MIBC Cohorts
Time Frame: 12, 18, 24 months
Landmark RFS, defined as RFS at specific timepoints.
12, 18, 24 months
Landmark Event-Free Survival (EFS) for MIBC Cohorts
Time Frame: 12, 18, 24 months
Landmark EFS, defined as EFS at specific timepoints.
12, 18, 24 months
Landmark Overall Survival (OS) for MIBC Cohorts
Time Frame: 12, 18, 24 months
Landmark OS, defined as OS at specific timepoints.
12, 18, 24 months
Progression Free Survival (PFS) for mUC Cohort Stage 1
Time Frame: 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.
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
Time Frame: 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.
Randomization to death from any cause, through the end of study (approximately 5-7 years)
Duration of Response (DOR) for mUC Cohort Stage 1
Time Frame: 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.
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
Time Frame: 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.
Baseline through end of study (approximately 5-7 years)
Percentage of Participants with Adverse Events for mUC Cohort Stage 1
Time Frame: Baseline to end of study (approximately 5-7 years)
Baseline to end of study (approximately 5-7 years)
Serum Concentration of Atezolizumab for mUC Cohort Stage 2
Time Frame: At pre-defined intervals from first administration of study drug up to approximately 5-7 years
At pre-defined intervals from first administration of study drug up to approximately 5-7 years
Serum Concentration of Enfortumab Vedotin for mUC Cohort Stage 2
Time Frame: At pre-defined intervals from first administration of study drug up to approximately 5-7 years
At pre-defined intervals from first administration of study drug up to approximately 5-7 years
Serum Concentration of Sacituzumab Govitecan for mUC Cohort Stage 2
Time Frame: At pre-defined intervals from first administration of study drug up to approximately 5-7 years
At pre-defined intervals from first administration of study drug up to approximately 5-7 years
Presence of ADAs to Atezolizumab for mUC Cohort Stage 2
Time Frame: 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.
Baseline to approximately 5-7 years
Percentage of Participants with Adverse Events for mUC Cohort Stage 2
Time Frame: Baseline to end of study (approximately 5-7 years)
Baseline to end of study (approximately 5-7 years)
Percentage of Participants with Adverse Events for MIBC Cohorts
Time Frame: Baseline to approximately 5-7 years
Baseline to approximately 5-7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2019

Primary Completion (Estimated)

December 6, 2024

Study Completion (Estimated)

November 27, 2027

Study Registration Dates

First Submitted

March 8, 2019

First Submitted That Met QC Criteria

March 8, 2019

First Posted (Actual)

March 11, 2019

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

March 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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