Urothelial Carcinoma
Conditions
Keywords
Urothelial carcinoma, Bladder cancer, Anti-PD-L1, Transitional carcinoma, Tecentriq, Atezolizumab, IMvigor130
Brief summary
A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy versus chemotherapy alone in participants with untreated advanced urothelial cancer.
Interventions
DRUGAtezolizumab
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.
DRUGCarboplatin
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.
DRUGGemcitabine
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.
OTHERPlacebo
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.
DRUGCisplatin
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment * Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (\</=) 2 * Histologically documented, locally advanced (T4b, any N; or any T, N2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed transitional cell carcinoma \[TCC\] or urothelial cell carcinoma \[UCC\] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra) * Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor PD-L1 expression prior to study enrollment; participants who have fewer than 15 unstained slides available at baseline (but no less than \[\<\] 10) may be eligible following discussion with the Medical Monitor * No prior chemotherapy for inoperable locally advanced or mUC * For participants who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval more than (\>) 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting * Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment * Measurable disease, as defined by RECIST v1.1 * Adequate hematologic and end-organ function * 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 6 months after the last dose of carboplatin, cisplatin, or gemcitabine or for 5 months after the last dose of atezolizumab * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
Exclusion criteria
* Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment * Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrolment * Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments * Participants with treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: \* Evaluable or measurable disease outside the CNS \* No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) \* No history of intracranial or spinal cord hemorrhage \* No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed \* No evidence of significant vasogenic edema \* No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 \* Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study \* Screening CNS radiographic study \>/=4 weeks since completion of radiotherapy or surgical resection and \>/=2 weeks since discontinuation of corticosteroids * Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents * Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 2 weeks prior to Cycle 1, Day 1 or anticipated requirement for systemic immunosuppressive medications during the study * Leptomeningeal disease * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Uncontrolled tumour-related pain or hypercalcemia * Significant cardiovascular disease including known left ventricular ejection fraction (LVEF) \<40% * Severe infections within 4 weeks before randomization or therapeutic oral or IV antibiotics within 2 weeks before randomization * Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis * Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1 * Life expectancy of \<12 weeks * Pregnant or lactating, or intending to become pregnant during the study * Serum albumin \<25 gram per liter (g/L) * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins * Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation * History of autoimmune disease * Participants with prior allogeneic stem cell or solid organ transplantation * History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan * Positive test for human immunodeficiency virus (HIV) * Active hepatitis B or hepatitis C * Active tuberculosis * Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm | Baseline up to first documented disease progression or death, whichever occurs first (up to approximately 35 months) | 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. |
| Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Baseline until death due to any cause (up to approximately 73 months) | OS is defined as the time from randomization to death due to any cause. |
| Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Baseline until death due to any cause (up to approximately 73 months) | OS is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months) | 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. |
| IRF-PFS | Randomization to first documented disease progression or death from any cause (up to 35 months) | 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. |
| OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Year 1 | Overall Survival (OS) Event Free Rate at 1 Year. |
| OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Year 1 | Overall Survival (OS) Event Free Rate at 1 Year. |
| PFS Event Free Rate | Year 1 | Progression Free Survival (PFS) Event Free Rate at Year 1 |
| 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 | Up to approximately 73 months | 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 EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm | Up to approximately 73 months | 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. |
| 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 | Up to approximately 73 months | 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. |
| 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 | Up to approximately 73 months | Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab Monotherapy Arm. |
| Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months) | 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. |
| Minimum 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 atezolizumab treatment, and study drug early discontinuation | Minimum atezolizumab serum concentration. |
| Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs) | Up to approximately 35 months | Percentage of participants with Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs). |
| Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 35 months) | 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. |
| Percentage of Participants With Grade 3-4 Adverse Events (AEs) | Baseline up to 93 months | Percentage of participants with Grade 3-4 Adverse Events (AEs) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
| Percentage of Participants With Grade 5 Adverse Events (AEs) | Baseline up to 93 months | Percentage of participants with Grade 5 Adverse Events (AEs) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
| Percentage of Participants With Serious Adverse Events (SAEs) | Baseline up to 93 months | Percentage of participants with Serious Adverse Events (SAEs) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
| Percentage of Participants With Adverse Events (AEs) Leading to Withdrawal of Any Study Treatment | Baseline up to 93 months | Percentage of participants with Adverse Events (AEs) leading to withdrawal of any study treatment assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
| Percentage of Participants With Atezolizumab-Specific Adverse Events of Special Interest (AESIs) | Baseline up to 93 months | Percentage of participants with atezolizumab-specific Adverse Events of Special Interest (AESIs) Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
| Maximum Atezolizumab Serum Concentration | Cycle 1 Day 1 | Maximum atezolizumab serum concentration. |
| Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months) | 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) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months) | 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. |
Countries
Australia, Belgium, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Czechia, Estonia, Finland, Georgia, Greece, Hong Kong, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovenia, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in 221 sites in 35 countries.
Pre-assignment details
Stage 1 included atezolizumab+gemcitabine+carboplatin arm or placebo+gemcitabine+carboplatin arm. Participants ineligible for cisplatin-based chemo were enrolled in this stage. Stage 2 included addition of atezolizumab monotherapy arm and allowed participants who were eligible for cisplatin-based chemotherapy. Study is considered Completed because all pre-planned study analyses have been preformed for primary and secondary endpoints.
Participants by arm
| Arm | Count |
|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin Participants received blinded placebo matched to atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). | 400 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Participants received blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). | 451 |
| Atezolizumab Monotherapy Eligible participants received open-label atezolizumab as monotherapy. | 362 |
| Total | 1,213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 303 | 332 | 272 |
| Overall Study | Lost to Follow-up | 10 | 13 | 6 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Deviation | 1 | 0 | 0 |
| Overall Study | Study Terminated By Sponsor | 47 | 76 | 60 |
| Overall Study | Symptomatic Deterioration | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 39 | 28 | 24 |
Baseline characteristics
| Characteristic | Placebo+Gemcitabine+Carboplatin/Cisplatin | Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Atezolizumab Monotherapy | Total |
|---|---|---|---|---|
| Age, Continuous | 66.4 Years STANDARD_DEVIATION 9.5 | 67.5 Years STANDARD_DEVIATION 9.7 | 67.0 Years STANDARD_DEVIATION 9.1 | 67.0 Years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 41 Participants | 40 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 350 Participants | 402 Participants | 311 Participants | 1063 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 8 Participants | 11 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Asian | 85 Participants | 90 Participants | 94 Participants | 269 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 5 Participants | 3 Participants | 15 Participants |
| Race (NIH/OMB) White | 305 Participants | 346 Participants | 260 Participants | 911 Participants |
| Sex: Female, Male Female | 102 Participants | 113 Participants | 82 Participants | 297 Participants |
| Sex: Female, Male Male | 298 Participants | 338 Participants | 280 Participants | 916 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 303 / 389 | 332 / 454 | 272 / 354 |
| other Total, other adverse events | 379 / 389 | 441 / 454 | 300 / 354 |
| serious Total, serious adverse events | 197 / 389 | 244 / 454 | 163 / 354 |
Outcome results
Primary
Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
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.
Time frame: Baseline up to first documented disease progression or death, whichever occurs first (up to approximately 35 months)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm | 6.34 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm | 8.18 Months |
Comparison: Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.007395% CI: [0.7, 0.96]Log Rank
Primary
Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
OS is defined as the time from randomization to death due to any cause.
Time frame: Baseline until death due to any cause (up to approximately 73 months)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 13.44 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 16.13 Months |
Comparison: Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.02395% CI: [0.73, 1]Regression, Cox
Primary
Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
OS is defined as the time from randomization to death due to any cause.
Time frame: Baseline until death due to any cause (up to approximately 73 months)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 13.34 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 15.21 Months |
Comparison: Stratification factors: PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.396895% CI: [0.82, 1.16]Log Rank
Secondary
Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
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.
Time frame: From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 8.15 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 9.13 Months |
Secondary
Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
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.
Time frame: From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 8.11 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 29.63 Months |
Secondary
Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
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.
Time frame: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 35 months)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 6.31 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 2.69 Months |
Comparison: Stratification factors: PD-L1 status and Bajorin risk score/presence of liver metastases and investigator choice of chemotherapy.p-value: 195% CI: [1.19, 1.69]Log Rank
Secondary
IRF-PFS
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.
Time frame: Randomization to first documented disease progression or death from any cause (up to 35 months)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | IRF-PFS | 6.34 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | IRF-PFS | 7.10 Months |
Comparison: Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.037395% CI: [0.73, 1.01]Regression, Cox
Secondary
Maximum Atezolizumab Serum Concentration
Maximum atezolizumab serum concentration.
Time frame: Cycle 1 Day 1
Population: The pharmacokinetic (PK)-evaluable population is defined as all participants dosed with atezolizumab who have at least one post-baseline PK result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Maximum Atezolizumab Serum Concentration | 379 μg/ mL | Standard Deviation 125 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Maximum Atezolizumab Serum Concentration | 390 μg/ mL | Standard Deviation 129 |
Secondary
Minimum Atezolizumab Serum Concentration
Minimum atezolizumab serum concentration.
Time frame: 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 atezolizumab treatment, and study drug early discontinuation
Population: The pharmacokinetic (PK)-evaluable population is defined as all participants dosed with atezolizumab who have at least one post-baseline PK result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 3 Day 1 | 122 μg/ mL | Standard Deviation 47.2 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 24 Day 1 | 244 μg/ mL | Standard Deviation 75.7 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 8 Day 1 | 216 μg/ mL | Standard Deviation 96.8 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 32 Day 1 | 259 μg/ mL | Standard Deviation 97.2 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 4 Day 1 | 153 μg/ mL | Standard Deviation 70.4 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Day 120 Post Dose of Last Blinded Atezo Trt | 18.8 μg/ mL | Standard Deviation 36.9 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 16 Day 1 | 235 μg/ mL | Standard Deviation 103 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Study Drug Early Discontinuation | 154 μg/ mL | Standard Deviation 102 |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 2 Day 1 | 79.8 μg/ mL | Standard Deviation 52.5 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Study Drug Early Discontinuation | 124 μg/ mL | Standard Deviation 83.8 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 2 Day 1 | 80.2 μg/ mL | Standard Deviation 46 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 3 Day 1 | 129 μg/ mL | Standard Deviation 66 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 4 Day 1 | 157 μg/ mL | Standard Deviation 63.4 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 8 Day 1 | 193 μg/ mL | Standard Deviation 79.8 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 16 Day 1 | 220 μg/ mL | Standard Deviation 79.8 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 24 Day 1 | 233 μg/ mL | Standard Deviation 92.5 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Cycle 32 Day 1 | 258 μg/ mL | Standard Deviation 60.5 |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Minimum Atezolizumab Serum Concentration | Day 120 Post Dose of Last Blinded Atezo Trt | 9.53 μg/ mL | Standard Deviation 12.7 |
Secondary
Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
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.
Time frame: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 44.8 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 48.1 Percentage of Participants |
Secondary
Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
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.
Time frame: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 44.4 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 24.2 Percentage of Participants |
Secondary
OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
Overall Survival (OS) Event Free Rate at 1 Year.
Time frame: Year 1
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 55.00 Percentage |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 60.00 Percentage |
Comparison: Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.150995% CI: [-1.82, 11.81]Z-test
Secondary
OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
Overall Survival (OS) Event Free Rate at 1 Year.
Time frame: Year 1
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 54.56 Percentage |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm | 57.91 Percentage |
Comparison: Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.376195% CI: [-4.08, 10.79]Z-test
Secondary
Percentage of Participants With Adverse Events (AEs) Leading to Withdrawal of Any Study Treatment
Percentage of participants with Adverse Events (AEs) leading to withdrawal of any study treatment assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Baseline up to 93 months
Population: The safety population was defined as participants who received any amount of any component of study treatment. Participants were analyzed according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Adverse Events (AEs) Leading to Withdrawal of Any Study Treatment | 36.3 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Adverse Events (AEs) Leading to Withdrawal of Any Study Treatment | 33.9 Percentage of Participants |
| Atezolizumab Monotherapy | Percentage of Participants With Adverse Events (AEs) Leading to Withdrawal of Any Study Treatment | 9.0 Percentage of Participants |
Secondary
Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)
Percentage of participants with Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs).
Time frame: Up to approximately 35 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs) | Baseline evaluable participants | 1.2 Percentage of participants |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs) | Post-baseline evaluable participants | 19.7 Percentage of participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs) | Baseline evaluable participants | 0.9 Percentage of participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs) | Post-baseline evaluable participants | 26.3 Percentage of participants |
Secondary
Percentage of Participants With Atezolizumab-Specific Adverse Events of Special Interest (AESIs)
Percentage of participants with atezolizumab-specific Adverse Events of Special Interest (AESIs) Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Baseline up to 93 months
Population: The safety population was defined as participants who received any amount of any component of study treatment. Participants were analyzed according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Atezolizumab-Specific Adverse Events of Special Interest (AESIs) | 53.3 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Atezolizumab-Specific Adverse Events of Special Interest (AESIs) | 35.5 Percentage of Participants |
| Atezolizumab Monotherapy | Percentage of Participants With Atezolizumab-Specific Adverse Events of Special Interest (AESIs) | 39.5 Percentage of Participants |
Secondary
Percentage of Participants With Grade 3-4 Adverse Events (AEs)
Percentage of participants with Grade 3-4 Adverse Events (AEs) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Baseline up to 93 months
Population: The safety population was defined as participants who received any amount of any component of study treatment. Participants were analyzed according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Grade 3-4 Adverse Events (AEs) | 84.1 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Grade 3-4 Adverse Events (AEs) | 84.6 Percentage of Participants |
| Atezolizumab Monotherapy | Percentage of Participants With Grade 3-4 Adverse Events (AEs) | 46.3 Percentage of Participants |
Secondary
Percentage of Participants With Grade 5 Adverse Events (AEs)
Percentage of participants with Grade 5 Adverse Events (AEs) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Baseline up to 93 months
Population: The safety population was defined as participants who received any amount of any component of study treatment. Participants were analyzed according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Grade 5 Adverse Events (AEs) | 7.5 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Grade 5 Adverse Events (AEs) | 5.7 Percentage of Participants |
| Atezolizumab Monotherapy | Percentage of Participants With Grade 5 Adverse Events (AEs) | 7.9 Percentage of Participants |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs)
Percentage of participants with Serious Adverse Events (SAEs) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Baseline up to 93 months
Population: The safety population was defined as participants who received any amount of any component of study treatment. Participants were analyzed according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Serious Adverse Events (SAEs) | 53.7 Percentage of Participants |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | Percentage of Participants With Serious Adverse Events (SAEs) | 50.6 Percentage of Participants |
| Atezolizumab Monotherapy | Percentage of Participants With Serious Adverse Events (SAEs) | 46.0 Percentage of Participants |
Secondary
PFS Event Free Rate
Progression Free Survival (PFS) Event Free Rate at Year 1
Time frame: Year 1
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | PFS Event Free Rate | 22.17 Percentage |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | PFS Event Free Rate | 30.47 Percentage |
Comparison: Stratification factors: Enrollment stage, PD-L1 status, Bajorin risk score/presence of liver metastases, and investigator choice of chemotherapy.p-value: 0.008395% CI: [-14.45, -2.13]Z-test
Secondary
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
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 frame: Up to approximately 73 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | 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 | 12.06 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | 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 | 32.07 Months |
Comparison: Strata are: Enrollment Stage, PD-L1 Status, BAJORIN Risk Factor Score and Stratum 4 for all participants.p-value: 0.054295% CI: [0.64, 1]Log Rank
Secondary
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 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.
Time frame: Up to approximately 73 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | 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 | 12.02 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | 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 | 23.20 Months |
Comparison: Strata are: PD-L1 Status, BAJORIN Risk Factor Score and Stratum 4 for all participants.p-value: 0.613995% CI: [0.74, 1.19]Log Rank
Secondary
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
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.
Time frame: Up to approximately 73 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | 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 | 15.74 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | 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 | 16.39 Months |
Comparison: Strata are: Enrollment Stage, PD-L1 Status, BAJORIN Risk Factor Score and Stratum 4 for all participants.p-value: 0.55495% CI: [0.86, 1.32]Log Rank
Secondary
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
Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab Monotherapy Arm.
Time frame: Up to approximately 73 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+Gemcitabine+Carboplatin/Cisplatin | 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 | 16.10 Months |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | 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 | 9.23 Months |
Comparison: Strata are: Enrollment Stage, PD-L1 Status, BAJORIN Risk Factor Score and Stratum 4 for all participants.p-value: 0.024195% CI: [1.03, 1.62]Log Rank