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

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ClinicalTrials.gov Identifier: NCT03869190
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : November 18, 2021
Sponsor:
Collaborator:
Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with cisplatin-ineligible 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: RO7122290 Drug: RO7121661 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 735 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 : November 1, 2024
Estimated Study Completion Date : November 9, 2024

Resource links provided by the National Library of Medicine


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.


Drug: RO7122290
RO7122290 will be administered by IV infusion at a dose of 250 mg on Day 1, 8, and 15 of each 21-day cycle.

Experimental: RO7121661 for mUC Cohort (Stage 1)
Participants will receive 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: RO7121661
RO7121661 will be administered by IV infusion at a dose of 2100 mg on Day 1 and 15 of each 21-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 MIBC Cohort 1 PD-L1+
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 + Tiragolumab for MIBC Cohort 1 PD-L1+
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 + RO7122290 for MIBC Cohort PD-L1+
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.


Drug: RO7122290
RO7122290 will be administered by IV infusion at a dose of 250 mg on Day 1, 8, and 15 of each 21-day cycle.

Active Comparator: Atezolizumab for MIBC Cohort 2 PD-L1-
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 + Tiragolumab for MIBC Cohort 2 PD-L1-
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 + RO7122290 for MIBC Cohort 2 PD-L1-
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.


Drug: RO7122290
RO7122290 will be administered by IV infusion at a dose of 250 mg on Day 1, 8, and 15 of each 21-day cycle.




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 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.

  2. pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts [ Time Frame: 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 :
  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 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.

  2. Overall Survival (OS) for mUC Cohort Stage 1 [ Time Frame: 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.

  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 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.

  5. Disease Control Rate (DCR) for mUC Cohort Stage 1 [ Time Frame: 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.

  6. Percentage of Participants with Adverse Events for mUC Cohort Stage 1 [ Time Frame: Baseline to end of study (approximately 4 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 4 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 4 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 4 years ]
  10. Presence of ADAs to Atezolizumab for mUC Cohort Stage 2 [ Time Frame: 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.

  11. Percentage of Participants with Adverse Events for mUC Cohort Stage 2 [ Time Frame: Baseline to end of study (approximately 4 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 4 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
  • Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate
  • 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:

  • Patients will be excluded from the Atezo + Tira arm within the MIBC Cohorts if they meet any of the additional criteria for that arm.
  • 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 in the MIBC Cohorts:

- Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening

Additional Exclusion Criteria for Atezo+RO7122290 Arm in the MIBC Cohorts:

- Clinically significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of study drug administration will be excluded.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03869190


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: WO39613 https://forpatients.roche.com/ 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
Show Show 27 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03869190    
Other Study ID Numbers: WO39613
First Posted: March 11, 2019    Key Record Dates
Last Update Posted: November 18, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Atezolizumab
Niraparib
Magrolimab
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological