Primary Outcomes:

Primary Outcome 1 - Measure: Objective Response Rate (ORR) for mUC Cohort Stage 1

Primary Outcome 1 - Time Frame: Baseline until disease progression or loss of clinical benefit (approximately 4 years)

Primary Outcome 2 - Measure: pCR for Muscle Invasive Bladder Cancer (MIBC) Cohorts

Primary Outcome 2 - Time Frame: Randomization to approximately 4 years

Condition:

• Urothelial Carcinoma
• Bladder Cancer

Eligibility

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.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No