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

• ClinicalTrials.gov Identifier: NCT03869190
• Recruitment Status: Recruiting
• First Posted: March 11, 2019
• Last Update Posted: March 28, 2023
• Sponsor: Hoffmann-La Roche
• Collaborator: Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Urothelial Carcinoma; Bladder Cancer	Drug: Atezolizumab; Drug: Enfortumab Vedotin; Drug: Niraparib; Drug: Magrolimab (Hu5F9-G4); Drug: Tiragolumab; Drug: Sacituzumab Govitecan; Drug: Tocilizumab; Drug: Cisplatin; Drug: Gemcitabine	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 645 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: June 1, 2019
• Estimated Primary Completion Date: December 6, 2024
• Estimated Study Completion Date: November 27, 2027

Arms and Interventions

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.	Drug: Atezolizumab; 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.	Drug: Atezolizumab; 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.; Drug: Enfortumab Vedotin; 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.	Drug: Atezolizumab; 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.; Drug: Niraparib; Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.
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.	Drug: Atezolizumab; 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.; Drug: Magrolimab (Hu5F9-G4); 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.
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.	Drug: Atezolizumab; 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.; Drug: Tiragolumab; 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.	Drug: Atezolizumab; 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.; Drug: Sacituzumab Govitecan; 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.	Drug: Atezolizumab; 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.; Drug: Tocilizumab; 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.	Drug: Atezolizumab; 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.	Drug: Atezolizumab; 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.; Drug: Enfortumab Vedotin; 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.	Drug: Atezolizumab; 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.; Drug: Sacituzumab Govitecan; Sacituzumab Govitecan will be administered at a dose of 10 mg/kg by IV on Day 1 and 8 of each 21-day cycle.
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.	Drug: Atezolizumab; 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.	Drug: Atezolizumab; 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.; Drug: Tiragolumab; 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.	Drug: Atezolizumab; 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.	Drug: Atezolizumab; 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.; Drug: Tiragolumab; 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.	Drug: Atezolizumab; 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.; Drug: Cisplatin; 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.; Drug: Gemcitabine; 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.	Drug: Atezolizumab; 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.; Drug: Tiragolumab; Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.; Drug: Cisplatin; 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.; Drug: Gemcitabine; 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.

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Percentage of Participants with Adverse Events for mUC Cohort Stage 1 [ Time Frame: Baseline to end of study (approximately 5-7 years) ]
7. 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 ]
8. 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 ]
9. 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 ]
10. 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.
11. Percentage of Participants with Adverse Events for mUC Cohort Stage 2 [ Time Frame: Baseline to end of study (approximately 5-7 years) ]
12. Landmark Recurrence-Free Survival (RFS) for MIBC Cohorts [ Time Frame: 12, 18, 24 months ]
    Landmark RFS, defined as RFS at specific timepoints.
13. Landmark Event-Free Survival (EFS) for MIBC Cohorts [ Time Frame: 12, 18, 24 months ]
    Landmark EFS, defined as EFS at specific timepoints.
14. Landmark Overall Survival (OS) for MIBC Cohorts [ Time Frame: 12, 18, 24 months ]
    Landmark OS, defined as OS at specific timepoints.
15. Percentage of Participants with Adverse Events for MIBC Cohorts [ Time Frame: Baseline to approximately 5-7 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Reference Study ID Number: WO39613 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Locations

United States, California

UCLA Department of Medicine; Recruiting

Los Angeles, California, United States, 90024

UCSF Comprehensive Cancer Ctr; Recruiting

San Francisco, California, United States, 94158

Stanford Cancer Center; Recruiting

Stanford, California, United States, 94305-5820

United States, Kentucky

University of Kentucky Chandler Medical Center; Recruiting

Lexington, Kentucky, United States, 40536

Norton Cancer Institute; Recruiting

Louisville, Kentucky, United States, 40202

United States, North Carolina

Levine Cancer Institute; Recruiting

Charlotte, North Carolina, United States, 28204

United States, Ohio

University Hospitals Cleveland Medical Center; Recruiting

Cleveland, Ohio, United States, 44106

Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

United States, Texas

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030-4009

France

Centre Francois Baclesse; Pharmacie; Recruiting

Caen, France, 14076

Centre Leon Berard; Suspended

Lyon, France, 69008

Institut régional du Cancer Montpellier; Recruiting

Montpellier, France, 34298

Institut Claudius Regaud; Radiotherapie; Recruiting

Toulouse, France, 31052

Gustave Roussy Cancer Campus; Completed

Villejuif, France, 94805

Greece

Alexandras General Hospital of Athens; Oncology Department; Completed

Athens, Greece, 115 28

Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine; Recruiting

Athens, Greece, 12462

Athens Medical Center; Dept. of Oncology; Recruiting

Athens, Greece, 151 25

University Hospital of Patras Medical Oncology; Withdrawn

Patras, Greece, 265 04

Korea, Republic of

Seoul National University Hospital; Completed

Seoul, Korea, Republic of, 03080

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 05505

Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine; Recruiting

Seoul, Korea, Republic of, 120-749

Spain

ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO; Recruiting

L?Hospitalet De Llobregat, Barcelona, Spain, 08908

Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas; Recruiting

Santiago de Compostela, LA Coruña, Spain, 15706

Clinica Universitaria de Navarra; Completed

Pamplona, Navarra, Spain, 31008

Hospital del Mar; Completed

Barcelona, Spain, 08003

Vall d?Hebron Institute of Oncology (VHIO), Barcelona; Recruiting

Barcelona, Spain, 08035

Hospital Clinic i Provincial; Servicio de Neurologia; Recruiting

Barcelona, Spain, 08036

Hospital Universitario Reina Sofia; Recruiting

Cordoba, Spain, 14008

Hospital General Universitario Gregorio Mara; Suspended

Madrid, Spain, 28009

MD Anderson Cancer Center; Suspended

Madrid, Spain, 28033

Hospital Universitario Fundacion Jimenez Diaz.; Recruiting

Madrid, Spain, 28040

Hospital Univ 12 de Octubre; Recruiting

Madrid, Spain, 28041

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC; Recruiting

Madrid, Spain, 28050

Hospital Clinico Universitario de Valencia; Recruiting

Valencia, Spain, 46010

Taiwan

National Taiwan University Hospital, Yun-Lin Branch; Recruiting

Huwei Township, Taiwan, 63247

Kaohsiung Medical University Chung-Ho Memorial Hospital; Recruiting

Kaohsiung City, Taiwan, 807

National Cheng Kung University Hospital; Recruiting

Tainan, Taiwan, 70457

Taipei Veterans General Hospital; Recruiting

Taipei City, Taiwan, 112

United Kingdom

Barts and The London; Recruiting

London, United Kingdom, EC1M 6BQ

The Christie NHS Foundation Trust; Withdrawn

Manchester, United Kingdom, M20 4BX

Churchill Hospital; Pharmacy Clinical Trials Office, Pharmacy Department; Recruiting

Oxford, United Kingdom, OX3 7LJ

Royal Marsden NHS Foundation Trust; Recruiting

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

Hoffmann-La Roche

Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03869190
• Other Study ID Numbers: WO39613
• First Posted: March 11, 2019
• Last Update Posted: March 28, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gemcitabine; Atezolizumab; Niraparib; Magrolimab; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents, Immunological