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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03869190

Collaborator

Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas (Other)

645

Enrollment

Locations

Arms

101.9

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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: Hu5F9-G4 Drug: Tiragolumab Drug: Sacituzumab Govitecan Drug: Tocilizumab Drug: Cisplatin Drug: Gemcitabine	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated 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 :

Jun 1, 2019

Anticipated Primary Completion Date :

Dec 6, 2024

Anticipated Study Completion Date :

Nov 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.	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.	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.	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 + Hu5F9-G4 for mUC Cohort (Stage 1) Participants will receive atezolizumab and 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.	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: 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.	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.	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.	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.	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.	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.	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+ 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+ 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- 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- 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 muscle invasive bladder cancer (MIBC) Cohort 3 Arm 1 Participants will receive 3 cycles of Cisplatin, Gemcitabine and Atezolizumab 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 muscle invasive bladder cancer (MIBC) Cohort 3 Arm 2 Participants will receive Cisplatin, Gemcitabine, Atezolizumab and Tiragolumab (Tira) 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

Objective Response Rate (ORR) for mUC Cohort Stage 1 [Baseline until disease progression or loss of clinical benefit (approximately 4 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.
pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts [Randomization to approximately 4 years]
pCR, defined as the proportion of participants with an absence of residual invasive cancer of the complete resected specimen.

Secondary Outcome Measures

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 4 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.
Overall Survival (OS) for mUC Cohort Stage 1 [Randomization to death from any cause, through the end of study (approximately 4 years)]
OS after randomization,defined as the time from randomization to death from any cause.
Overall Survival (at specific time-points) for mUC Cohort Stage 1 [12 months]
OS rate at specific timepoints, defined as the proportion of patients who have not experienced death from any cause at that timepoint.
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 4 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.
Disease Control Rate (DCR) for mUC Cohort Stage 1 [Baseline through end of study (approximately 4 years)]
Disease control, defined as stable disease >= 18 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1.
Percentage of Participants with Adverse Events for mUC Cohort Stage 1 [Baseline to end of study (approximately 4 years)]
Serum Concentration of Atezolizumab for mUC Cohort Stage 2 [At pre-defined intervals from first administration of study drug up to approximately 4 years]
Serum Concentration of Enfortumab Vedotin for mUC Cohort Stage 2 [At pre-defined intervals from first administration of study drug up to approximately 4 years]
Serum Concentration of Sacituzumab Govitecan for mUC Cohort Stage 2 [At pre-defined intervals from first administration of study drug up to approximately 4 years]
Presence of ADAs to Atezolizumab for mUC Cohort Stage 2 [Baseline to approximately 4 years]
For drugs for which ADA formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline.
Percentage of Participants with Adverse Events for mUC Cohort Stage 2 [Baseline to end of study (approximately 4 years)]
Landmark Recurrence-Free Survival (RFS) for MIBC Cohorts [12, 18, 24 months]
Landmark RFS, defined as RFS at specific timepoints.
Landmark Event-Free Survival (EFS) for MIBC Cohorts [12, 18, 24 months]
Landmark EFS, defined as EFS at specific timepoints.
Landmark Overall Survival (OS) for MIBC Cohorts [12, 18, 24 months]
Landmark OS, defined as OS at specific timepoints.
Percentage of Participants with Adverse Events for MIBC Cohorts [Baseline to approximately 4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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

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

Locations

	Site	City	State	Country	Postal Code
1	UCLA Department of Medicine	Los Angeles	California	United States	90024
2	UCSF Comprehensive Cancer Ctr	San Francisco	California	United States	94158
3	Stanford Cancer Center	Stanford	California	United States	94305-5820
4	University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536
5	Norton Cancer Institute	Louisville	Kentucky	United States	40202
6	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
7	Cleveland Clinic	Cleveland	Ohio	United States	44195
8	Centre Francois Baclesse; Pharmacie	Caen		France	14076
9	Centre Leon Berard	Lyon		France	69008
10	Institut régional du Cancer Montpellier	Montpellier		France	34298
11	Institut Claudius Regaud; Radiotherapie	Toulouse		France	31052
12	Gustave Roussy Cancer Campus	Villejuif		France	94805
13	Alexandras General Hospital of Athens; Oncology Department	Athens		Greece	115 28
14	Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine	Athens		Greece	12462
15	Athens Medical Center; Dept. of Oncology	Athens		Greece	151 25
16	University Hospital of Patras Medical Oncology	Patras		Greece	265 04
17	Seoul National University Hospital	Seoul		Korea, Republic of	03080
18	Asan Medical Center	Seoul		Korea, Republic of	05505
19	Severance Hospital; Yonsei Cancer Center; Yonsei University College of Medicine	Seoul		Korea, Republic of	120-749
20	ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO	L'Hospitalet de Llobregat	Barcelona	Spain	08908
21	Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas	Santiago de Compostela	LA Coruña	Spain	15706
22	Clinica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
23	Hospital del Mar	Barcelona		Spain	08003
24	Vall d´Hebron Institute of Oncology (VHIO), Barcelona	Barcelona		Spain	08035
25	Hospital Clinic i Provincial; Servicio de Neurologia	Barcelona		Spain	08036
26	Hospital Universitario Reina Sofia	Cordoba		Spain	14008
27	Hospital General Universitario Gregorio Mara	Madrid		Spain	28009
28	MD Anderson Cancer Center	Madrid		Spain	28033
29	Hospital Universitario Fundacion Jimenez Diaz.	Madrid		Spain	28040
30	Hospital Univ 12 de Octubre	Madrid		Spain	28041
31	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid		Spain	28050
32	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
33	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City		Taiwan	807
34	National Cheng Kung University Hospital	Tainan		Taiwan	70457
35	Barts and The London	London		United Kingdom	EC1M 6BQ
36	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
37	Churchill Hospital; Pharmacy Clinical Trials Office, Pharmacy Department	Oxford		United Kingdom	OX3 7LJ
38	Royal Marsden NHS Foundation Trust	Sutton		United Kingdom	SM2 5PT