Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Carboplatin

Gemcitabine

Cisplatin

Atezolizumab

Immunoglobulins

Antimetabolites

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Participants will receive blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).

Participants will receive blinded placebo matched to atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).

Eligible participants will receive open-label atezolizumab as monotherapy.

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1. In specific circumstances treatment may continue beyond disease progression.

Carboplatin will be administered at doses to achieve area under the concentration-time curve (AUC) of 4.5 milligram per milliliter into minute (mg/mL\*min) by IV infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1 or unacceptable toxicity.

Gemcitabine will be administered at a dose of 1000 milligrams per square meter (mg/m\^2) by IV infusion on Day 1 and Day 8 of each 21-day cycle, until investigator-assessed disease progression per RECIST v1.1 or unacceptable toxicity.

Placebo matched to atezolizumab will be administered by IV infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1. In specific circumstances treatment may continue beyond disease progression.

Placebo

Cisplatin will be administered at a dose of 70 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1 or unacceptable toxicity.

Clinical Trials

A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy versus chemotherapy alone in participants with untreated advanced urothelial cancer.

Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever occurs first.

OS is defined as the time from randomization to death due to any cause.

Objective response rate (ORR) is defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), observed on two assessments \>= 28 days apart per RECIST v1.1, based on investigator assessment. The analysis population for ORR will be all randomized participants with measurable disease at baseline.

Duration of response (DOR) is defined for participants with an objective response as the time from the first documented objective response to documented disease progression per RECIST v1.1, based on investigator assessment, or death due to any cause, whichever occurs first.

Independent review facility PFS (IRF-PFS) is defined as the time from randomization to the first documented disease progression as determined by blinded independent central review with use of RECIST v1.1, or death due to any cause, whichever occurs first.

Overall Survival (OS) Event Free Rate at 1 Year.

Progression Free Survival (PFS) Event Free Rate at Year 1

Time to deterioration in global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm.

Time to deterioration in global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in the Placebo+Chemo Arm versus Atezolizumab Monotherapy Arm.

Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm.

Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab Monotherapy Arm.

Maximum atezolizumab serum concentration.

Minimum atezolizumab serum concentration.

Percentage of participants with Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs).

Hoffmann-La Roche

Serious \& other adverse events reported based on safety population, which included patients who received any amount of any component of study treatment. There were 6 patients randomized to Atezo monotherapy after approval of Protocol version 6 who received open-label Atezo and chemo, and were pooled with patients in Atezo+chemo for safety analyses. All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized patients.

Participants received blinded placebo matched to atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).

Placebo+Gemcitabine+Carboplatin/Cisplatin (Arm C)

Participants received blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).

Atezolizumab+Gemcitabine+Carboplatin/Cisplatin (Arm A)

Eligible participants received open-label atezolizumab as monotherapy.

Atezolizumab Monotherapy (Arm B)

Placebo+Gemcitabine+Carboplatin/Cisplatin

Atezolizumab+Gemcitabine+Carboplatin/Cisplatin

Atezolizumab Monotherapy

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Communications

Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.

The ITT population was defined as all participants randomized to the Atezolizumab+Gemcitabine+Carboplatin/Cisplatin arm or the Placebo+Gemcitabine+Carboplatin/Cisplatin arm in Stages 1 and 2, whether or not the assigned study treatment was received.

Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm

Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Stratification factors: PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.

The ITT population includes only participants concurrently enrolled in Stage 2 and only those who had been randomized at the time of approval of Protocol WO30070 v6.

Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

The ITT population was defined as all participants randomized to the Atezolizumab+Gemcitabine+Carboplatin/Cisplatin arm or the Placebo+Gemcitabine+Carboplatin/Cisplatin arm in Stages 1 and 2, whether or not the assigned study treatment was received. The measurable disease populations were defined as participants in the respective ITT populations with at least one measurable lesion according to RECIST v1.1 based on investigator assessment.

Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

The ITT population includes only participants concurrently enrolled in Stage 2 and only those who had been randomized at the time of approval of Protocol WO30070 v6. The measurable disease populations were defined as participants in the respective ITT populations with at least one measurable lesion according to RECIST v1.1 based on investigator assessment.

Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

The duration of response (DOR)-evaluable population is defined as participants with an objective response in the Atezolizumab+Gemcitabine+Carboplatin/Cisplatin arm or the Placebo+Gemcitabine+Carboplatin/Cisplatin arm in Stages 1 and 2.

Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

The duration of response (DOR)-evaluable population is defined as participants with an objective response in the the ITT population which included only participants concurrently enrolled in Stage 2 and only those who had been randomized at the time of approval of Protocol WO30070 v6.

Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

IRF-PFS

The ITT population was defined as all participants randomized to the Atezolizumab+Gemcitabine+Carboplatin/Cisplatin or the Placebo+Gemcitabine+Carboplatin/Cisplatin arm in Stages 1 and 2, whether or not the assigned study treatment was received.

OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

PFS Event Free Rate

Strata are: Enrollment Stage, PD-L1 Status, BAJORIN Risk Factor Score and Stratum 4 for all participants.

The patient reported outcome (PRO)-evaluable population is defined as participants in the ITT populations for comparisons of the Placebo+Chemo Arm versus Atezolizumab+Chemo Arm who have a baseline and at least one post-baseline assessment. The ITT population for the comparison of Atezo+Chemo Arm vs. Placebo+Chemo Arm included participants enrolled in Stage 1 and Stage 2, which consisted of 451 paarticipants in the Atezo+Chemo Arm and 400 participants in the Placebo+Chemo Arm.

Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm

Strata are: PD-L1 Status, BAJORIN Risk Factor Score and Stratum 4 for all participants.

Evaluable population defined as patients in ITT for comparisons of Placebo+Chemo vs. Atezo Mono who have a baseline and at least one post-baseline assessment. ITT for comparison of Atezo Mono vs. Placebo+Chemo consisted of 360 patients enrolled in Atezo Mono in Stage 2. Although a total of 400 patients were randomized to Placebo+Chemo throughout study, only 359 patients who were concurrently enrolled into this arm in Stage 2 and prior to Protocol v6 were included in Placebo+Chemo of this ITT.

Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm

Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm

Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm

The pharmacokinetic (PK)-evaluable population is defined as all participants dosed with atezolizumab who have at least one post-baseline PK result.

Maximum Atezolizumab Serum Concentration

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

Cycle 8 Day 1

Cycle 16 Day 1

Cycle 24 Day 1

Cycle 32 Day 1

Day 120 Post Dose of Last Blinded Atezo Trt

Study Drug Early Discontinuation

Minimum Atezolizumab Serum Concentration

Baseline evaluable participants

Post-baseline evaluable participants

The baseline ADA-evaluable population included participants who had a baseline ADA result. The post-baseline ADA-evaluable population included participants who had received at least one dose of the study treatment and who had at least one post-baseline ADA result.

Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)

Stratification factors: PD-L1 status and Bajorin risk score/presence of liver metastases and investigator choice of chemotherapy.

Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Percentage of Participants With Adverse Events (AEs) Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma	NCT02807636	Urothelial Carc...	Atezolizumab Carboplatin Gemcitabine Placebo Cisplatin	18 Years -	Hoffmann-La Roche
Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma	NCT02807636	Urothelial Carc...	Atezolizumab Carboplatin Gemcitabine Placebo Cisplatin	18 Years -	Hoffmann-La Roche

Spots Global Cancer Trial Database for transitional carcinoma