Safety and Pharmacology Study of Atezolizumab Alone and in Combination With Bacille Calmette-Guérin (BCG) in High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Participants

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02792192
• Collaborator: (none)
• Enrollment: 24
• Locations: 8
• Arms: 4
• Actual Duration (Months): 51.5
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase Ib/II study is designed to assess the safety, tolerability, pharmacokinetics, immunogenicity, patient reported outcomes (PROs), and preliminary anti-tumor activity of atezolizumab administered by intravenous (IV) infusion alone and in combination with intravesical BCG in high-risk NMIBC participants. The study will be conducted in following cohorts: Cohort 1A, Cohort 1B, Cohort 2, and Cohort 3. Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) every 3 weeks (q3w) for a maximum of 96 weeks. BCG will be administered to evaluate dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD). De-escalation will be allowed for up to three dose levels of BCG (full dose [50 mg], 66 percent [%] of a full dose, and 33% of a full dose [Cohort 1B only]). After the MTD or MAD is determined for Cohort 1B, this dose will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3, unless the MTD is determined to be 33% of a full BCG dose. If MTD is determined to be 33% of a full BCG dose, then, no participants will be enrolled into Cohorts 2 and 3 until an assessment of the safety and activity of the combination of atezolizumab plus 33% of a full BCG dose is completed.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Atezolizumab; Biological: Bacille Calmette-Guérin	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib/II, Open-Label Study of the Safety and Pharmacology of Atezolizumab Administered With or Without Bacille Calmette-Guérin in Patients With High-Risk Non-Muscle-Invasive Bladder Cancer
• Actual Study Start Date: Jun 13, 2016
• Actual Primary Completion Date: Sep 29, 2020
• Actual Study Completion Date: Sep 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC) Participants will receive atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedule specified in respective arm.; Other Names: MPDL3280A
Experimental: Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC) During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedule specified in respective arm.; Other Names: MPDL3280A ; Biological: Bacille Calmette-Guérin; For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).; Other Names: OncoTICE®
Experimental: Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC) During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedule specified in respective arm.; Other Names: MPDL3280A ; Biological: Bacille Calmette-Guérin; For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).; Other Names: OncoTICE®
Experimental: Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC) During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedule specified in respective arm.; Other Names: MPDL3280A ; Biological: Bacille Calmette-Guérin; For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).; Other Names: OncoTICE®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events [From Baseline up to end of study (up to approximately 4.3 years)]

   Percentage of participants with at least one adverse event during the study.

2. Cohort 1B: Percentage of Participants With DLTs of BCG [Days 1-21]

   Percentage of participants with dose-limiting toxicities (DLT) of BCG in Cohort 1B.

3. Cohort 1B: MAD of BCG [Days 1-21]

   Maximum administered dose (MAD) of BCG.

4. Percentage of Participants With Complete Response (CR) as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 6 [6 months]

   CR at 6 months after the start of study treatment as assessed by the investigator on the basis of cystoscopic assessment and urine cytology.

Secondary Outcome Measures

1. Percentage of Participants With CR as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 3 [3 months]

   CR at the 3-month disease assessment, evaluated by both cystoscopy and cytology.

2. Duration of CR, as Assessed on the Basis of Cystoscopy and Urine Cytology [From first occurence of a documented CR until the time of recurrence of NMIBC or death from any cause (up to approximately 4.3 years)]

   Duration of CR will be defined for participants with a CR as the time from the first occurrence of a documented complete response to recurrence of high-grade NMIBC or death from any cause.

3. Percentage of Participants With Recurrence-Free Survival (RFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [6, 12 and 18 months]

   RFS rate at 6, 12, and 18 months, defined as the proportion of patients who are alive and free of persistent/recurrent high-grade NMIBC.

4. Bladder-Intact Disease-Free Survival (DFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [From first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer-related death, or cystectomy or death from any cause (up to approximately 4.3 years)]

   Bladder-intact DFS was defined as the time from the first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer-related death, or cystectomy.

5. Progression-Free Survival (PFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [Time from first study treatment to the first occurrence of progression to muscle-invasive disease or death from any cause (up to approximately 4.3 years)]

   PFS, defined as the time from the first study treatment to the first occurrence of progression to muscle-invasive disease based on cystoscopy and urine cytology or death from any cause.

6. Cystectomy-Free Survival (CFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [Time from first study treatment to cystectomy or death from any cause (up to approximately 4.3 years)]

   Cystectomy-free survival, defined as from start of study treatment to bladder removal for any cause or death from any cause.

7. Overall Survival [Time from first study treatment to death from any cause (up to approximately 4.3 years)]

8. Maximum Observed Serum Concentration of Atezolizumab (Cmax) [Cycle 1 Day 1 post-dose (Cycle length=21 days)]

   Maximum observed serum concentration of Atezolizumab (Cmax)

9. Minimum Observed Serum Concentration of Atezolizumab (Cmin) [Pre-dose (0 hr) on Day 1 of Cycles 2, 3, 4 and 8 (Cycle length=21 days)]

   Minimum observed serum concentration of atezolizumab (Cmin)

10. Percentage of Participants With Anti-Therapeutic Antibody (ADA) Response to Atezolizumab [Pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24 (Cycle length=21 days), end of atezolizumab treatment (up to 96 weeks), 120 days after end of atezolizumab treatment (up to 113 weeks)]

    Percentage of participants with anti-therapeutic antibody (ADA) response to atezolizumab.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed non-muscle-invasive transitional cell carcinoma (TCC) of the bladder with carcinoma in-situ (CIS)

• High-risk NMIBC defined by the following:

BCG-unresponsive NMIBC:

Persistence of high-grade CIS at 6 months following an adequate course of BCG; or Stage/grade progression at 3 months after induction BCG; or Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs less than (<) 6 months after the last exposure to BCG

BCG-relapsing NMIBC:

Recurrence of high-grade CIS after achieving a disease-free state following induction of an adequate course of BCG that occurs greater than or equal to (>/=) 6 months after the last exposure to BCG

Very high-risk (VHR) BCG-naïve NMIBC:

VHR NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater than [>] 3 centimeters [cm]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1, G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial carcinoma

• For BCG-unresponsive and BCG-relapsing NMIBC, participants must have received an adequate course of BCG

• Resection of all pTa/pT1 papillary disease

• No prior radiation to bladder or pelvic region

• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (</=) 2;

• Life expectancy >/=12 weeks

• Adequate hematologic and end-organ function

• Creatinine clearance >/=30 milliliters per minute (mL/min) (calculated using the Cockcroft-Gault formula)

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of study drug. Women must refrain from donating eggs during this same period.

• For men receiving BCG: Agreement to remain abstinent (refrain from sexual intercourse) or use a condom

• Tumor tissue biopsy within 60 days prior to study entry or availability of an archival specimen obtained within 60 days of study screening

Exclusion Criteria:

• Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer

• Any malignancy within 5 years prior to Cycle 1, Day 1

• History of autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonitis

• Signs or symptoms of infection within 2 weeks prior to the first dose of study treatment

• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of study treatment

• Treatment with any approved anti-cancer therapy within 3 weeks prior to the first dose of study treatment

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to the first dose of study treatment

• Pregnant or lactating women, or women intending to become pregnant during the study

• Prior allogeneic stem cell or solid organ transplantation

• Positive test for human immunodeficiency virus (HIV)

• Active hepatitis B or C and/or tuberculosis

• Severe infections within 28 days prior to the first dose of study treatment

• Significant cardiovascular disease

• Major surgical procedure other than for diagnosis within 4 weeks prior to the first dose of study treatment, or anticipation of need for a major surgical procedure during the course of the study

• Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study

• History of prior significant toxicity or intolerance to BCG requiring discontinuation of treatment

• History of prior systemic BCG infection

• History of immunosuppression, or conditions associated with congenital or acquired immune deficiency

• Concurrent febrile illness, urinary tract infection, or gross hematuria

• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies

• Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first dose of study treatment

• Treatment with systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Univ.	Stanford	California	United States	94305
2	University of Chicago Medical Center	Chicago	Illinois	United States	60637
3	Johns Hopkins Kimmel Cancer Center, Office of Research Administration	Baltimore	Maryland	United States	21205
4	The Montefiore Medical Center & The Albert Einstein College of Medicine; Department of Urology	Bronx	New York	United States	10461
5	Duke University	Durham	North Carolina	United States	27705
6	Ohio State University	Columbus	Ohio	United States	43210
7	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
8	VA Portland Healthcare System	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 10, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02792192
• Other Study ID Numbers: WO29635
• First Posted: Jun 7, 2016
• Last Update Posted: Oct 28, 2021
• Last Verified: Sep 1, 2021

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Atezolizumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled only in Cohort 1 of this study. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1 (BCG-unresponsive cohort), as the study had met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Period Title: Overall Study
STARTED	12	12	0	0
COMPLETED	0	1	0	0
NOT COMPLETED	12	11	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)	Total
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	Total of all reporting groups
Overall Participants	12	12	0	0	24
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	72.7 (13.2)	72.1 (9.0)	72.4 (11.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 16.7%	2 Infinity
Male	12 100%	10 83.3%	22 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 8.3%	0 NaN	0 NaN	1 4.2%
Not Hispanic or Latino	12 100%	11 91.7%	0 NaN	0 NaN	23 95.8%
Unknown or Not Reported	0 0%	0 0%	0 NaN	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 NaN	0 NaN	0 0%
Asian	0 0%	0 0%	0 NaN	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 NaN	0 NaN	0 0%
Black or African American	3 25%	1 8.3%	0 NaN	0 NaN	4 16.7%
White	8 66.7%	10 83.3%	0 NaN	0 NaN	18 75%
More than one race	0 0%	1 8.3%	0 NaN	0 NaN	1 4.2%
Unknown or Not Reported	1 8.3%	0 0%	0 NaN	0 NaN	1 4.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events
Description	Percentage of participants with at least one adverse event during the study.
Time Frame	From Baseline up to end of study (up to approximately 4.3 years)

Outcome Measure Data

Analysis Population Description

All participants were included in the safety-evaluable population, defined as all participants treated with any amount of study drug. Participants were enrolled only in Cohort 1 of this study. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12	12	0	0
Number [Percentage of participants]	100 833.3%	100 833.3%

2. Primary Outcome

Title	Cohort 1B: Percentage of Participants With DLTs of BCG
Description	Percentage of participants with dose-limiting toxicities (DLT) of BCG in Cohort 1B.
Time Frame	Days 1-21

Outcome Measure Data

Analysis Population Description

All participants were included in the safety-evaluable population, defined as all participants treated with any amount of study drug. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)
Arm/Group Description	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12
Number [Percentage of participants]	16.7 139.2%

3. Primary Outcome

Title	Cohort 1B: MAD of BCG
Description	Maximum administered dose (MAD) of BCG.
Time Frame	Days 1-21

Outcome Measure Data

Analysis Population Description

All participants were included in the safety-evaluable population, defined as all participants treated with any amount of study drug. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)
Arm/Group Description	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12
Number [mg]	50

4. Primary Outcome

Title	Percentage of Participants With Complete Response (CR) as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 6
Description	CR at 6 months after the start of study treatment as assessed by the investigator on the basis of cystoscopic assessment and urine cytology.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12	12	0	0
Number (95% Confidence Interval) [Percentage of participants]	33.3 277.5%	41.7 347.5%

5. Secondary Outcome

Title	Percentage of Participants With CR as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 3
Description	CR at the 3-month disease assessment, evaluated by both cystoscopy and cytology.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12	12	0	0
Number (95% Confidence Interval) [Percentage of participants]	16.7 139.2%	41.7 347.5%

6. Secondary Outcome

Title	Duration of CR, as Assessed on the Basis of Cystoscopy and Urine Cytology
Description	Duration of CR will be defined for participants with a CR as the time from the first occurrence of a documented complete response to recurrence of high-grade NMIBC or death from any cause.
Time Frame	From first occurence of a documented CR until the time of recurrence of NMIBC or death from any cause (up to approximately 4.3 years)

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	4	5	0	0
Participants With CR at 6 Months	6.80	NA
Participants With CR at 3 Months	NA	NA

7. Secondary Outcome

Title	Percentage of Participants With Recurrence-Free Survival (RFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
Description	RFS rate at 6, 12, and 18 months, defined as the proportion of patients who are alive and free of persistent/recurrent high-grade NMIBC.
Time Frame	6, 12 and 18 months

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC. Data for RFS was not collected as the study was stopped early.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	0	0	0	0

8. Secondary Outcome

Title	Bladder-Intact Disease-Free Survival (DFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
Description	Bladder-intact DFS was defined as the time from the first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer-related death, or cystectomy.
Time Frame	From first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer-related death, or cystectomy or death from any cause (up to approximately 4.3 years)

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC. Data for DFS was not collected as the study was stopped early.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	0	0	0	0

9. Secondary Outcome

Title	Progression-Free Survival (PFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
Description	PFS, defined as the time from the first study treatment to the first occurrence of progression to muscle-invasive disease based on cystoscopy and urine cytology or death from any cause.
Time Frame	Time from first study treatment to the first occurrence of progression to muscle-invasive disease or death from any cause (up to approximately 4.3 years)

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC. Data for PFS was not collected as the study was stopped early.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	0	0	0	0

10. Secondary Outcome

Title	Cystectomy-Free Survival (CFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
Description	Cystectomy-free survival, defined as from start of study treatment to bladder removal for any cause or death from any cause.
Time Frame	Time from first study treatment to cystectomy or death from any cause (up to approximately 4.3 years)

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC. Data for CFS was not collected as the study was stopped early.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	0	0	0	0

11. Secondary Outcome

Title	Overall Survival
Time Frame	Time from first study treatment to death from any cause (up to approximately 4.3 years)

Outcome Measure Data

Analysis Population Description

Efficacy evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1), as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC. Data for OS was not collected as the study was stopped early.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	0	0	0	0

12. Secondary Outcome

Title	Maximum Observed Serum Concentration of Atezolizumab (Cmax)
Description	Maximum observed serum concentration of Atezolizumab (Cmax)
Time Frame	Cycle 1 Day 1 post-dose (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12	11	0	0
Mean (Standard Deviation) [μg/mL]	413 (109)	310 (63.7)

13. Secondary Outcome

Title	Minimum Observed Serum Concentration of Atezolizumab (Cmin)
Description	Minimum observed serum concentration of atezolizumab (Cmin)
Time Frame	Pre-dose (0 hr) on Day 1 of Cycles 2, 3, 4 and 8 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description

PK evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12	12	0	0
Cycle 2 Day 1	92.2 (14.9)	90.5 (42.6)
Cycle 3 Day 1	143 (26.1)	133 (74.4)
Cycle 4 Day 1	174 (38.4)	162 (91.1)
Cycle 8 Day 1	211 (59.4)	192 (117)

14. Secondary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibody (ADA) Response to Atezolizumab
Description	Percentage of participants with anti-therapeutic antibody (ADA) response to atezolizumab.
Time Frame	Pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24 (Cycle length=21 days), end of atezolizumab treatment (up to 96 weeks), 120 days after end of atezolizumab treatment (up to 113 weeks)

Outcome Measure Data

Analysis Population Description

ADA evaluable participants. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)	Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)	Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)	Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.	During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.	During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Measure Participants	12	12	0	0
Baseline prevalence	9.1 75.8%	0 0%
Post-Baseline Treatment-Emergent	8.3 69.2%	41.7 347.5%

Adverse Events

Time Frame	From the first study drug to the data cutoff date: 29 September 2020 (up to 4.3 years)
Adverse Event Reporting Description	The Safety Evaluable Population includes all participants treated with any amount of study drug (atezolizumab or BCG). Participants were enrolled only in Cohort 1 of this study. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1, as the study met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.
Arm/Group Title	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)		Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)		Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)		Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
Arm/Group Description	Participants received atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.		During BCG induction course (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants received atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.		During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.		During BCG induction course (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants were to receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
All Cause Mortality
	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)		Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)		Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)		Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/12 (0%)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)		Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)		Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)		Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		3/12 (25%)		0/0 (NaN)		0/0 (NaN)
Blood and lymphatic system disorders
Blood loss anaemia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Cardiac disorders
Atrial fibrillation	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
General disorders
Complication associated with device	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Pyrexia	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Infections and infestations
Coronavirus infection	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Pneumonia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Pyelonephritis	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Renal and urinary disorders
Haematuria	0/12 (0%)	0	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Urinary retention	0/12 (0%)	0	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)		Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)		Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)		Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		12/12 (100%)		0/0 (NaN)		0/0 (NaN)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Lymphadenopathy	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Cardiac disorders
Atrial fibrillation	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Endocrine disorders
Hypothyroidism	0/12 (0%)	0	3/12 (25%)	3	3/0 (Infinity)	3	3/0 (Infinity)	3
Eye disorders
Dry eye	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Eye irritation	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Gastrointestinal disorders
Abdominal distension	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Abdominal pain	0/12 (0%)	0	3/12 (25%)	3	3/0 (Infinity)	3	3/0 (Infinity)	3
Constipation	1/12 (8.3%)	1	3/12 (25%)	3	3/0 (Infinity)	3	3/0 (Infinity)	3
Diarrhoea	0/12 (0%)	0	2/12 (16.7%)	3	2/0 (Infinity)	3	2/0 (Infinity)	3
Dry mouth	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Dysphagia	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Lip oedema	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Nausea	0/12 (0%)	0	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Stomatitis	0/12 (0%)	0	1/12 (8.3%)	2	1/0 (Infinity)	2	1/0 (Infinity)	2
General disorders
Chills	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Fatigue	7/12 (58.3%)	9	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Influenza like illness	0/12 (0%)	0	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Injury associated with device	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Mucosal inflammation	1/12 (8.3%)	2	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Oedema	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Oedema peripheral	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Peripheral swelling	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pyrexia	2/12 (16.7%)	2	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Hepatobiliary disorders
Hepatic steatosis	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Immune system disorders
Seasonal allergy	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Infections and infestations
Atypical mycobacterial pneumonia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Candida infection	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Cystitis	1/12 (8.3%)	2	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Ear infection	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Gastroenteritis	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Influenza	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Nasopharyngitis	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Pustule	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Sinusitis	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Tooth infection	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Upper respiratory tract infection	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Urinary tract infection	1/12 (8.3%)	1	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Investigations
Alanine aminotransferase increased	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Amylase increased	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Aspartate aminotransferase increased	1/12 (8.3%)	1	2/12 (16.7%)	4	2/0 (Infinity)	4	2/0 (Infinity)	4
Blood alkaline phosphatase increased	0/12 (0%)	0	1/12 (8.3%)	2	1/0 (Infinity)	2	1/0 (Infinity)	2
Blood creatinine increased	0/12 (0%)	0	2/12 (16.7%)	8	2/0 (Infinity)	8	2/0 (Infinity)	8
Lymphocyte count decreased	0/12 (0%)	0	2/12 (16.7%)	5	2/0 (Infinity)	5	2/0 (Infinity)	5
Platelet count decreased	0/12 (0%)	0	1/12 (8.3%)	9	1/0 (Infinity)	9	1/0 (Infinity)	9
Weight decreased	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Weight increased	0/12 (0%)	0	1/12 (8.3%)	2	1/0 (Infinity)	2	1/0 (Infinity)	2
Metabolism and nutrition disorders
Hyperglycaemia	0/12 (0%)	0	2/12 (16.7%)	6	2/0 (Infinity)	6	2/0 (Infinity)	6
Hyperkalaemia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Hyponatraemia	0/12 (0%)	0	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)	0	1/12 (8.3%)	2	1/0 (Infinity)	2	1/0 (Infinity)	2
Back pain	1/12 (8.3%)	1	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Bone pain	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Flank pain	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pain in extremity	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Nervous system disorders
Anosmia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Dizziness	2/12 (16.7%)	2	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Headache	1/12 (8.3%)	2	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hypoaesthesia	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Neuropathy peripheral	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Syncope	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Tremor	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Psychiatric disorders
Anxiety	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Depression	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Renal and urinary disorders
Bladder pain	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Bladder spasm	1/12 (8.3%)	1	5/12 (41.7%)	5	5/0 (Infinity)	5	5/0 (Infinity)	5
Chronic kidney disease	0/12 (0%)	0	1/12 (8.3%)	7	1/0 (Infinity)	7	1/0 (Infinity)	7
Cystitis noninfective	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dysuria	2/12 (16.7%)	2	4/12 (33.3%)	6	4/0 (Infinity)	6	4/0 (Infinity)	6
Haematuria	0/12 (0%)	0	5/12 (41.7%)	5	5/0 (Infinity)	5	5/0 (Infinity)	5
Micturition urgency	0/12 (0%)	0	2/12 (16.7%)	4	2/0 (Infinity)	4	2/0 (Infinity)	4
Nocturia	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pollakiuria	0/12 (0%)	0	6/12 (50%)	8	6/0 (Infinity)	8	6/0 (Infinity)	8
Urge incontinence	0/12 (0%)	0	1/12 (8.3%)	2	1/0 (Infinity)	2	1/0 (Infinity)	2
Urinary incontinence	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Cough	2/12 (16.7%)	2	2/12 (16.7%)	2	2/0 (Infinity)	2	2/0 (Infinity)	2
Dysphonia	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dyspnoea	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Hypoxia	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Laryngeal haemorrhage	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Nasal congestion	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Paranasal sinus hypersecretion	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Productive cough	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Skin and subcutaneous tissue disorders
Actinic keratosis	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Alopecia	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Dermatitis	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Erythema	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Hyperhidrosis	1/12 (8.3%)	1	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Pruritus	1/12 (8.3%)	1	1/12 (8.3%)	2	1/0 (Infinity)	2	1/0 (Infinity)	2
Rash	4/12 (33.3%)	5	2/12 (16.7%)	3	2/0 (Infinity)	3	2/0 (Infinity)	3
Rash macular	0/12 (0%)	0	2/12 (16.7%)	4	2/0 (Infinity)	4	2/0 (Infinity)	4
Rash maculo-papular	2/12 (16.7%)	2	3/12 (25%)	3	3/0 (Infinity)	3	3/0 (Infinity)	3
Skin lesion	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1
Vascular disorders
Hypertension	1/12 (8.3%)	1	0/12 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0
Phlebitis	0/12 (0%)	0	1/12 (8.3%)	1	1/0 (Infinity)	1	1/0 (Infinity)	1

Limitations/Caveats

Participants were enrolled only in Cohort 1 of this study. The Sponsor decided not to enroll participants in Cohorts 2 and 3 after the enrollment of 24 patients in Cohort 1 (BCG-unresponsive cohort), as the study had met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.