A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)

• ClinicalTrials.gov Identifier: NCT02108652
• Recruitment Status: Completed
• First Posted: April 9, 2014
• Results First Posted: January 4, 2017
• Last Update Posted: March 28, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bladder Cancer
• Intervention: Drug: Atezolizumab
• Enrollment: 310

Participant Flow

Recruitment Details	The study is considered "Completed" because the planned study activities and analyses have been performed.
Pre-assignment Details	The analysis included data up to cutoff date 28 February 2023.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Period Title: Overall Study
Started	310
Completed	0
Not Completed	310
Reason Not Completed
Death	253
Lost to Follow-up	2
Withdrawal by Subject	16
Study Terminated By Sponsor	31
Non-Compliance	1
Physician Decision	6
Progression Of Disease	1

Baseline Characteristics

Arm/Group Title		Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description		Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Baseline Participants		310
Baseline Analysis Population Description		Cohort 2 Safety Evaluable Population included all participants who received any amount of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	310 participants
		65.6 (10.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	310 participants
	Female	69 22.3%
	Male	241 77.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Description	Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 objective response-evaluable population included Intent-to-treat (ITT) participants who had measurable disease per RECIST v1.1 at baseline. Cohort 2 ITT population included all participants from Cohort 2 who received any amount of study drug.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	15.8; (11.9 to 20.4)

2. Primary Outcome

Title	Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According Modified RECIST
Description	Tumor response was assessed by the investigator according to modified RECIST. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 objective response-evaluable population.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	19.7; (15.4 to 24.6)

3. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1
Description	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	49
Median (Full Range); Unit of Measure: months
	NA [1]; (2.1 to NA)

[1]

The median DOR and upper limit for the Full Range were not reached at a median follow up of 21.060 months on study.

4. Secondary Outcome

Title	DOR as Assessed by the Investigator According to RECIST v1.1
Description	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	51
Median (Full Range); Unit of Measure: months
	20.50; (2.1 to 20.5)

5. Secondary Outcome

Title	DOR as Assessed by the Investigator According to Modified RECIST
Description	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the investigator according to modified RECIST. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	61
Median (Full Range); Unit of Measure: months
	20.50; (2.1 to 20.5)

6. Secondary Outcome

Title	Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1
Description	Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Unit of Measure: percentage of participants
	88.4

7. Secondary Outcome

Title	Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1
Description	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Median (95% Confidence Interval); Unit of Measure: months
	2.10; (2.07 to 2.14)

8. Secondary Outcome

Title	Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1
Description	Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Unit of Measure: percentage of participants
	89.7

9. Secondary Outcome

Title	PFS as Assessed by the Investigator According to RECIST v1.1
Description	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Median (95% Confidence Interval); Unit of Measure: months
	2.10; (2.07 to 2.14)

10. Secondary Outcome

Title	Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to Modified RECIST
Description	Tumor response was assessed by the investigator according to modified RECIST. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Unit of Measure: percentage of participants
	87.1

11. Secondary Outcome

Title	PFS as Assessed by the Investigator According to Modified RECIST
Description	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the investigator according to modified RECIST. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Median (95% Confidence Interval); Unit of Measure: months
	2.56; (2.14 to 3.61)

12. Secondary Outcome

Title	Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1
Description	Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.
Time Frame	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 objective response-evaluable population.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	16.5; (12.5 to 21.1)

13. Secondary Outcome

Title	Percentage of Participants Who Died
Description	The percentage of participants who died from any cause was reported.
Time Frame	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Unit of Measure: percentage of participants
	72.9

14. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from start of treatment to the time of death from any cause on study.
Time Frame	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Median (95% Confidence Interval); Unit of Measure: months
	7.9; (6.7 to 9.3)

15. Secondary Outcome

Title	Percentage of Participants Alive at 1-year
Description	[Not Specified]
Time Frame	1-year

Outcome Measure Data

Analysis Population Description

Cohort 2 ITT Population

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	310
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	36.9; (31.4 to 42.3)

16. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Atezolizumab
Description	[Not Specified]
Time Frame	Pre-dose (0 hours) and 30 minutes post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Cohort 2 pharmacokinetic (PK) evaluable population was defined as participants who received any dose of atezolizumab treatment and had PK data at timepoints that were sufficient to determine PK parameters. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	300
Mean (Standard Deviation); Unit of Measure: microgram(s)/milliliter (mcg/mL)
	364 (120)

17. Secondary Outcome

Title	Minimum Serum Concentration (Cmin) of Atezolizumab
Description	[Not Specified]
Time Frame	Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Cohort 2 PK evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome. "n" = participants who were evaluable at specified timepoint.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	303
Mean (Standard Deviation); Unit of Measure: mcg/mL
Pre-dose Cycle 1 (n=303)	0.0252 (0.429)
Pre-dose Cycle 2 (n=269)	74.2 (29.9)
Pre-dose Cycle 3 (n=146)	120.0 (59.5)
Pre-dose Cycle 4 (n=186)	147.0 (77.7)
Pre-dose Cycle 8 (n=108)	188.0 (76.1)

18. Secondary Outcome

Title	Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab
Description	[Not Specified]
Time Frame	Day 1 of all cycles (Cycle length = 21 days) and at treatment discontinuation (data cutoff date 04 July 2016, up to maximum length of follow-up of 24.48 months)

Outcome Measure Data

Analysis Population Description

Cohort 2 Safety Evaluable Population. Here, number of participants analyzed = participants for whom ATA samples were available.

Arm/Group Title	Cohort 2: Participants With Second-line or Beyond Treatments
Arm/Group Description:	Participants who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Overall Number of Participants Analyzed	276
Measure Type: Number; Unit of Measure: percentage of participants
	42.4

Adverse Events

Time Frame	First dose of study drug until data cutoff date 28 February 2023 (up to approximately 105 months)
Adverse Event Reporting Description	All-Cause Mortality was assessed for all enrolled participants, Serious and Other Adverse Events were assessed in the safety population.
Arm/Group Title	MPDL3280A COHORT2 INFUSION
Arm/Group Description	[Not Specified]
All-Cause Mortality
	MPDL3280A COHORT2 INFUSION
	Affected / at Risk (%)
Total	253/310 (81.61%)
Serious Adverse Events
	MPDL3280A COHORT2 INFUSION
	Affected / at Risk (%)	# Events
Total	155/310 (50.00%)
Blood and lymphatic system disorders
ANAEMIA † 1	2/310 (0.65%)	2
LEUKOCYTOSIS † 1	1/310 (0.32%)	1
LYMPH NODE PAIN † 1	2/310 (0.65%)	2
Cardiac disorders
ARRHYTHMIA † 1	0/310 (0.00%)	0
ATRIAL FIBRILLATION † 1	1/310 (0.32%)	1
CARDIAC ARREST † 1	0/310 (0.00%)	0
CARDIAC FAILURE † 1	0/310 (0.00%)	0
CORONARY ARTERY DISEASE † 1	1/310 (0.32%)	1
MYOCARDIAL INFARCTION † 1	0/310 (0.00%)	0
PERICARDIAL EFFUSION † 1	1/310 (0.32%)	1
Ear and labyrinth disorders
VERTIGO † 1	0/310 (0.00%)	0
Endocrine disorders
HYPOTHYROIDISM † 1	1/310 (0.32%)	1
Gastrointestinal disorders
ABDOMINAL HERNIA † 1	1/310 (0.32%)	1
ABDOMINAL PAIN † 1	3/310 (0.97%)	3
ABDOMINAL PAIN LOWER † 1	0/310 (0.00%)	0
ANAL INCONTINENCE † 1	1/310 (0.32%)	1
AUTOIMMUNE COLITIS † 1	0/310 (0.00%)	0
COLITIS † 1	3/310 (0.97%)	3
COLITIS ISCHAEMIC † 1	1/310 (0.32%)	1
DIARRHOEA † 1	2/310 (0.65%)	2
GASTROINTESTINAL HAEMORRHAGE † 1	1/310 (0.32%)	1
ILEUS † 1	1/310 (0.32%)	1
INTESTINAL OBSTRUCTION † 1	2/310 (0.65%)	2
INTESTINAL PERFORATION † 1	0/310 (0.00%)	0
LARGE INTESTINAL OBSTRUCTION † 1	1/310 (0.32%)	1
NAUSEA † 1	3/310 (0.97%)	4
RECTAL HAEMORRHAGE † 1	1/310 (0.32%)	1
SMALL INTESTINAL OBSTRUCTION † 1	6/310 (1.94%)	9
SUBILEUS † 1	1/310 (0.32%)	1
VOMITING † 1	1/310 (0.32%)	1
General disorders
ASTHENIA † 1	3/310 (0.97%)	3
CHILLS † 1	1/310 (0.32%)	1
FATIGUE † 1	3/310 (0.97%)	3
GAIT DISTURBANCE † 1	1/310 (0.32%)	1
HAEMORRHAGIC CYST † 1	1/310 (0.32%)	1
MALAISE † 1	1/310 (0.32%)	1
NON-CARDIAC CHEST PAIN † 1	1/310 (0.32%)	1
PAIN † 1	4/310 (1.29%)	6
PERFORMANCE STATUS DECREASED † 1	1/310 (0.32%)	1
PYREXIA † 1	8/310 (2.58%)	8
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME † 1	1/310 (0.32%)	1
Hepatobiliary disorders
CHOLECYSTITIS † 1	2/310 (0.65%)	2
HEPATITIS † 1	1/310 (0.32%)	1
HYPERBILIRUBINAEMIA † 1	0/310 (0.00%)	0
LIVER DISORDER † 1	0/310 (0.00%)	0
Immune system disorders
HYPERSENSITIVITY † 1	0/310 (0.00%)	0
Infections and infestations
ABDOMINAL INFECTION † 1	1/310 (0.32%)	1
BACTERAEMIA † 1	2/310 (0.65%)	2
BILIARY SEPSIS † 1	0/310 (0.00%)	0
BRONCHITIS † 1	1/310 (0.32%)	1
BURSITIS INFECTIVE STAPHYLOCOCCAL † 1	0/310 (0.00%)	0
CELLULITIS † 1	1/310 (0.32%)	1
CELLULITIS OF MALE EXTERNAL GENITAL ORGAN † 1	1/310 (0.32%)	1
DEVICE RELATED INFECTION † 1	1/310 (0.32%)	2
DIVERTICULITIS † 1	2/310 (0.65%)	2
GASTROENTERITIS † 1	1/310 (0.32%)	1
INFLUENZA † 1	0/310 (0.00%)	0
KIDNEY INFECTION † 1	2/310 (0.65%)	3
MENINGOENCEPHALITIS HERPETIC † 1	0/310 (0.00%)	0
PNEUMONIA † 1	7/310 (2.26%)	7
POST PROCEDURAL INFECTION † 1	0/310 (0.00%)	0
PULMONARY SEPSIS † 1	1/310 (0.32%)	1
PYELONEPHRITIS † 1	4/310 (1.29%)	4
RETROPERITONEAL INFECTION † 1	1/310 (0.32%)	1
SEPSIS † 1	9/310 (2.90%)	9
SKIN INFECTION † 1	1/310 (0.32%)	1
STAPHYLOCOCCAL INFECTION † 1	1/310 (0.32%)	1
URINARY TRACT INFECTION † 1	23/310 (7.42%)	24
URINARY TRACT INFECTION PSEUDOMONAL † 1	1/310 (0.32%)	1
UROSEPSIS † 1	3/310 (0.97%)	3
VASCULAR DEVICE INFECTION † 1	1/310 (0.32%)	1
Injury, poisoning and procedural complications
FALL † 1	1/310 (0.32%)	1
FRACTURE † 1	1/310 (0.32%)	1
HIP FRACTURE † 1	2/310 (0.65%)	2
ILIUM FRACTURE † 1	1/310 (0.32%)	1
JOINT INJURY † 1	0/310 (0.00%)	0
LOWER LIMB FRACTURE † 1	1/310 (0.32%)	1
POST PROCEDURAL HAEMORRHAGE † 1	1/310 (0.32%)	1
SPINAL COMPRESSION FRACTURE † 1	1/310 (0.32%)	1
STOMA SITE HAEMORRHAGE † 1	1/310 (0.32%)	1
TOXICITY TO VARIOUS AGENTS † 1	1/310 (0.32%)	1
VASCULAR PSEUDOANEURYSM RUPTURED † 1	1/310 (0.32%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	2/310 (0.65%)	2
ASPARTATE AMINOTRANSFERASE INCREASED † 1	3/310 (0.97%)	3
BLOOD ALKALINE PHOSPHATASE INCREASED † 1	1/310 (0.32%)	1
BLOOD BILIRUBIN INCREASED † 1	1/310 (0.32%)	1
BLOOD CREATINE PHOSPHOKINASE INCREASED † 1	0/310 (0.00%)	0
BLOOD CREATININE INCREASED † 1	2/310 (0.65%)	2
PLATELET COUNT DECREASED † 1	1/310 (0.32%)	1
WHITE BLOOD CELL COUNT DECREASED † 1	1/310 (0.32%)	1
Metabolism and nutrition disorders
DEHYDRATION † 1	6/310 (1.94%)	6
FAILURE TO THRIVE † 1	1/310 (0.32%)	1
HYPERCALCAEMIA † 1	4/310 (1.29%)	5
HYPERKALAEMIA † 1	1/310 (0.32%)	1
HYPONATRAEMIA † 1	5/310 (1.61%)	5
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	1/310 (0.32%)	1
BACK PAIN † 1	6/310 (1.94%)	10
BONE PAIN † 1	2/310 (0.65%)	2
FLANK PAIN † 1	1/310 (0.32%)	1
MUSCULAR WEAKNESS † 1	2/310 (0.65%)	2
OSTEOPOROSIS † 1	1/310 (0.32%)	1
PATHOLOGICAL FRACTURE † 1	0/310 (0.00%)	0
RHABDOMYOLYSIS † 1	0/310 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA PANCREAS † 1	0/310 (0.00%)	0
BASAL CELL CARCINOMA † 1	1/310 (0.32%)	1
MALIGNANT MELANOMA † 1	1/310 (0.32%)	1
TUMOUR ASSOCIATED FEVER † 1	1/310 (0.32%)	1
Nervous system disorders
ATAXIA † 1	1/310 (0.32%)	1
CEREBRAL HAEMORRHAGE † 1	1/310 (0.32%)	2
CEREBROVASCULAR ACCIDENT † 1	2/310 (0.65%)	2
DIPLEGIA † 1	1/310 (0.32%)	1
ENCEPHALOPATHY † 1	3/310 (0.97%)	3
PARAPLEGIA † 1	1/310 (0.32%)	1
SYNCOPE † 1	2/310 (0.65%)	2
TRANSIENT ISCHAEMIC ATTACK † 1	0/310 (0.00%)	0
Product Issues
THROMBOSIS IN DEVICE † 1	0/310 (0.00%)	0
Psychiatric disorders
CONFUSIONAL STATE † 1	3/310 (0.97%)	3
DELIRIUM † 1	2/310 (0.65%)	2
HALLUCINATION † 1	1/310 (0.32%)	1
MENTAL STATUS CHANGES † 1	0/310 (0.00%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY † 1	6/310 (1.94%)	6
BLADDER PERFORATION † 1	0/310 (0.00%)	0
CHRONIC KIDNEY DISEASE † 1	1/310 (0.32%)	1
HAEMATURIA † 1	12/310 (3.87%)	12
HYDRONEPHROSIS † 1	3/310 (0.97%)	3
HYDROURETER † 1	1/310 (0.32%)	1
RENAL FAILURE † 1	1/310 (0.32%)	1
URETERIC OBSTRUCTION † 1	1/310 (0.32%)	1
URINARY RETENTION † 1	1/310 (0.32%)	1
URINARY TRACT OBSTRUCTION † 1	1/310 (0.32%)	1
Reproductive system and breast disorders
PELVIC PAIN † 1	2/310 (0.65%)	2
PENILE PAIN † 1	1/310 (0.32%)	1
VAGINAL HAEMORRHAGE † 1	1/310 (0.32%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNOEA † 1	10/310 (3.23%)	12
HAEMOPTYSIS † 1	2/310 (0.65%)	2
HICCUPS † 1	1/310 (0.32%)	1
HYPOXIA † 1	2/310 (0.65%)	2
PLEURAL EFFUSION † 1	1/310 (0.32%)	1
PNEUMONITIS † 1	5/310 (1.61%)	5
PNEUMOTHORAX † 1	1/310 (0.32%)	1
PULMONARY ARTERY THROMBOSIS † 1	0/310 (0.00%)	0
PULMONARY EMBOLISM † 1	8/310 (2.58%)	8
RESPIRATORY DISTRESS † 1	0/310 (0.00%)	0
RESPIRATORY FAILURE † 1	0/310 (0.00%)	0
Skin and subcutaneous tissue disorders
DERMATITIS PSORIASIFORM † 1	0/310 (0.00%)	0
ERYTHEMA † 1	1/310 (0.32%)	1
RASH MACULO-PAPULAR † 1	1/310 (0.32%)	1
Social circumstances
IMMOBILE † 1	1/310 (0.32%)	1
Surgical and medical procedures
RENAL STONE REMOVAL † 1	1/310 (0.32%)	1
URETERAL STENT INSERTION † 1	1/310 (0.32%)	1
Vascular disorders
DEEP VEIN THROMBOSIS † 1	3/310 (0.97%)	3
EMBOLISM † 1	1/310 (0.32%)	1
HAEMATOMA † 1	0/310 (0.00%)	0
HYPOTENSION † 1	1/310 (0.32%)	1
1 Term from vocabulary, MedDRA 26.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MPDL3280A COHORT2 INFUSION
	Affected / at Risk (%)	# Events
Total	287/310 (92.58%)
Blood and lymphatic system disorders
ANAEMIA † 1	56/310 (18.06%)	72
Gastrointestinal disorders
ABDOMINAL PAIN † 1	44/310 (14.19%)	54
CONSTIPATION † 1	85/310 (27.42%)	102
DIARRHOEA † 1	69/310 (22.26%)	103
DRY MOUTH † 1	24/310 (7.74%)	25
NAUSEA † 1	86/310 (27.74%)	114
VOMITING † 1	61/310 (19.68%)	83
General disorders
ASTHENIA † 1	23/310 (7.42%)	37
CHILLS † 1	34/310 (10.97%)	37
FATIGUE † 1	164/310 (52.90%)	228
INFLUENZA LIKE ILLNESS † 1	17/310 (5.48%)	65
OEDEMA PERIPHERAL † 1	52/310 (16.77%)	63
PAIN † 1	27/310 (8.71%)	34
PYREXIA † 1	70/310 (22.58%)	90
Infections and infestations
NASOPHARYNGITIS † 1	19/310 (6.13%)	25
UPPER RESPIRATORY TRACT INFECTION † 1	23/310 (7.42%)	28
URINARY TRACT INFECTION † 1	62/310 (20.00%)	94
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	16/310 (5.16%)	24
BLOOD ALKALINE PHOSPHATASE INCREASED † 1	19/310 (6.13%)	20
BLOOD CREATININE INCREASED † 1	22/310 (7.10%)	38
WEIGHT DECREASED † 1	28/310 (9.03%)	34
Metabolism and nutrition disorders
DECREASED APPETITE † 1	89/310 (28.71%)	110
HYPERGLYCAEMIA † 1	17/310 (5.48%)	30
HYPOALBUMINAEMIA † 1	20/310 (6.45%)	26
HYPOKALAEMIA † 1	19/310 (6.13%)	24
HYPOMAGNESAEMIA † 1	16/310 (5.16%)	18
HYPONATRAEMIA † 1	20/310 (6.45%)	25
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	65/310 (20.97%)	98
BACK PAIN † 1	57/310 (18.39%)	83
FLANK PAIN † 1	23/310 (7.42%)	30
MUSCULAR WEAKNESS † 1	31/310 (10.00%)	44
MYALGIA † 1	17/310 (5.48%)	20
PAIN IN EXTREMITY † 1	40/310 (12.90%)	55
Nervous system disorders
DIZZINESS † 1	26/310 (8.39%)	29
HEADACHE † 1	30/310 (9.68%)	37
Psychiatric disorders
ANXIETY † 1	18/310 (5.81%)	18
INSOMNIA † 1	22/310 (7.10%)	22
Renal and urinary disorders
HAEMATURIA † 1	49/310 (15.81%)	76
Respiratory, thoracic and mediastinal disorders
COUGH † 1	59/310 (19.03%)	86
DYSPNOEA † 1	55/310 (17.74%)	74
NASAL CONGESTION † 1	21/310 (6.77%)	22
Skin and subcutaneous tissue disorders
DRY SKIN † 1	20/310 (6.45%)	21
PRURITUS † 1	54/310 (17.42%)	77
RASH † 1	40/310 (12.90%)	53
1 Term from vocabulary, MedDRA 26.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Holm JS, Funt SA, Borch A, Munk KK, Bjerregaard AM, Reading JL, Maher C, Regazzi A, Wong P, Al-Ahmadie H, Iyer G, Tamhane T, Bentzen AK, Herschend NO, De Wolf S, Snyder A, Merghoub T, Wolchok JD, Nielsen M, Rosenberg JE, Bajorin DF, Hadrup SR. Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma. Nat Commun. 2022 Apr 11;13(1):1935. doi: 10.1038/s41467-022-29342-0.

Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.

Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM, Cipolla CK, Bluth MJ, Chaim J, Al-Ahmadie H, Snyder A, Carlo MI, Solit DB, Berger MF, Funt S, Wolchok JD, Iyer G, Bajorin DF, Callahan MK, Rosenberg JE. Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. J Clin Oncol. 2018 Jun 10;36(17):1685-1694. doi: 10.1200/JCO.2017.75.7740. Epub 2018 Feb 28.

Perez-Gracia JL, Loriot Y, Rosenberg JE, Powles T, Necchi A, Hussain SA, Morales-Barrera R, Retz MM, Niegisch G, Duran I, Theodore C, Grande E, Shen X, Wang J, Nelson B, Derleth CL, van der Heijden MS. Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens. Eur Urol. 2018 Mar;73(3):462-468. doi: 10.1016/j.eururo.2017.11.023. Epub 2017 Dec 20. Erratum In: Eur Urol. 2019 Mar;75(3):e82-e83.

Necchi A, Joseph RW, Loriot Y, Hoffman-Censits J, Perez-Gracia JL, Petrylak DP, Derleth CL, Tayama D, Zhu Q, Ding B, Kaiser C, Rosenberg JE. Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study. Ann Oncol. 2017 Dec 1;28(12):3044-3050. doi: 10.1093/annonc/mdx518.

Snyder A, Nathanson T, Funt SA, Ahuja A, Buros Novik J, Hellmann MD, Chang E, Aksoy BA, Al-Ahmadie H, Yusko E, Vignali M, Benzeno S, Boyd M, Moran M, Iyer G, Robins HS, Mardis ER, Merghoub T, Hammerbacher J, Rosenberg JE, Bajorin DF. Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: An exploratory multi-omic analysis. PLoS Med. 2017 May 26;14(5):e1002309. doi: 10.1371/journal.pmed.1002309. eCollection 2017 May.

Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Duran I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thastrom A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8. Erratum In: Lancet. 2017 Aug 26;390(10097):848.

Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02108652
• Other Study ID Numbers: GO29293 (Cohort 2); IMvigor 210 ( Other Identifier: Genentech Inc. ); 2013-005486-39 ( EudraCT Number )
• First Submitted: April 7, 2014
• First Posted: April 9, 2014
• Results First Submitted: July 1, 2016
• Results First Posted: January 4, 2017
• Last Update Posted: March 28, 2024