Urothelial Cancer
Conditions
Brief summary
The purpose of this study is to determine whether an investigational immunotherapy nivolumab in combination with ipilimumab or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating participants with previously untreated inoperable or metastatic urothelial cancer.
Interventions
DRUGGemcitabine
Specified Dose on Specified Days
DRUGCisplatin
Specified Dose on Specified Days
BIOLOGICALNivolumab
Specified Dose on Specified Days
BIOLOGICALIpilimumab
Specified Dose on Specified Days
DRUGCarboplatin
Specified Dose on Specified Days
Sponsors
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer (TCC) of the urothelium involving the renal pelvis, ureter, bladder or urethra * No prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer (UC) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Women and men must agree to follow specific methods of contraception, if applicable
Exclusion criteria
* Disease that is suitable for local therapy administered with curative intent * Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study | From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) | This measure looks at how long participants who cannot receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand if the treatment can help people who are unable to receive cisplatin chemotherapy live longer. |
| Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study | From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) | This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer. |
| Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-eligible Participants for Sub-study | From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) | This measure looks at how long people who can receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the sub-study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people eligible for cisplatin live longer without their cancer progressing. |
| Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study | From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) | This measure looks at how long people who are able to receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the sub-study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand if the treatment can help people who are eligible for cisplatin chemotherapy live longer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in All Randomized Participants for Primary Study | From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) | This measure looks at how long all participants live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help all participants in the study live longer. |
| Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-ineligible Randomized Participants for Primary Study | From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) | This measure looks at how long people who cannot receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the primary study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people unable to receive cisplatin live longer without their cancer progressing. |
| Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Participants for Primary Study | From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) | This measure looks at how long people with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a lab test) live without their cancer getting worse after being assigned to a treatment group in the primary study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people with PD-L1 positive tumors live longer without their cancer progressing. |
| Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in All Randomized Participants for Primary Study | From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) | This measure looks at how long all participants in the primary study live without their cancer getting worse after being assigned to a treatment group. Progression-Free Survival (PFS) is defined as the time from when a participant is assigned to a treatment group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment the participant received. These experts use standard rules (called RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand whether the treatment can help participants live longer without their cancer progressing. |
| Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, Week 120, Week 144, Week 156, Week 168, Week 180 and Week 192 | The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It includes a global health status score, which is measured on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much. Responses are combined and converted to scores ranging from 0 to 100. A high score for global health status or health-related quality of life (HRQoL) indicates a high overall HRQoL. |
| Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, and Week 120 | The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It includes a global health status score, which is measured on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much. Responses are combined and converted to scores ranging from 0 to 100. A high score for global health status or health-related quality of life (HRQoL) indicates a high overall HRQoL. |
| Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study | From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months) | This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a lab test called immunohistochemistry or IHC) live without their cancer getting worse after being assigned to a treatment group in the sub-study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. |
| Overall Survival (OS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study | From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months) | This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the sub-study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer. The results are reviewed by independent experts who do not know which treatment each participant received, using standard criteria for measuring tumor response. |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Czechia, Denmark, Finland, France, Germany, Greece, Israel, Italy, Japan, Mexico, Netherlands, Norway, Peru, Poland, Romania, Russia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
The study was conducted as a primary study and a sub-study. In the primary study, 706 participants were randomized, and 673 participants received treatment. Of these 673 treated participants, 3 were randomized in the sub-study. In the sub-study, 608 participants were randomized, and 605 participants received treatment. Of these 605 treated participants, 13 were randomized in the primary study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment 1 Participants received Nivolumab 1 mg/kg plus Ipilimumab 3 mg/kg every three weeks (Q3W) for up to 4 doses followed by Nivolumab monotherapy 480 mg every 4 weeks (Q4W) - Primary Study | 349 |
| Treatment 2 Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study | 357 |
| Treatment 3 Participants received Nivolumab 360 mg in combination with Standard of Care treatment every 3 weeks (Q3W) for up to 6 cycles followed by Nivolumab monotherapy 480 mg every 4 weeks (Q4W) - Sub-study | 304 |
| Treatment 4 Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Sub-study | 304 |
| Total | 1,314 |
Baseline characteristics
| Characteristic | Treatment 1 | Treatment 2 | Treatment 3 | Treatment 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 229 Participants | 230 Participants | 154 Participants | 156 Participants | 769 Participants |
| Age, Categorical Between 18 and 65 years | 120 Participants | 127 Participants | 150 Participants | 148 Participants | 545 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 18 Participants | 38 Participants | 33 Participants | 113 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 151 Participants | 118 Participants | 119 Participants | 546 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 167 Participants | 188 Participants | 148 Participants | 152 Participants | 655 Participants |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 79 Participants | 105 Participants | 75 Participants | 63 Participants | 322 Participants |
| Race/Ethnicity, Customized Black Or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 14 Participants | 16 Participants | 17 Participants | 13 Participants | 60 Participants |
| Race/Ethnicity, Customized White | 253 Participants | 232 Participants | 211 Participants | 225 Participants | 921 Participants |
| Sex: Female, Male Female | 80 Participants | 88 Participants | 68 Participants | 70 Participants | 306 Participants |
| Sex: Female, Male Male | 269 Participants | 269 Participants | 236 Participants | 234 Participants | 1008 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 257 / 349 | 294 / 357 | 172 / 304 | 193 / 304 |
| other Total, other adverse events | 322 / 345 | 309 / 328 | 298 / 304 | 295 / 301 |
| serious Total, serious adverse events | 264 / 345 | 170 / 328 | 168 / 304 | 130 / 301 |
Outcome results
Primary
Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study
This measure looks at how long people who are able to receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the sub-study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand if the treatment can help people who are eligible for cisplatin chemotherapy live longer.
Time frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
Population: All Cisplatin-eligible Randomized Participants - Sub-study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study | 21.72 Months |
| Treatment 2 | Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study | 18.86 Months |
p-value: 0.017195% CI: [0.63, 0.96]Log Rank
Primary
Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study
This measure looks at how long participants who cannot receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand if the treatment can help people who are unable to receive cisplatin chemotherapy live longer.
Time frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
Population: All Cisplatin-ineligible Randomized Participants - Primary Study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study | 19.06 Months |
| Treatment 2 | Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study | 13.21 Months |
p-value: 0.003295% CI: [0.64, 0.97]Log Rank
Primary
Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study
This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer.
Time frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
Population: All PD-L1 \>= 1% Randomized Participants - Primary Study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study | 16.30 Months |
| Treatment 2 | Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study | 14.36 Months |
Primary
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-eligible Participants for Sub-study
This measure looks at how long people who can receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the sub-study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people eligible for cisplatin live longer without their cancer progressing.
Time frame: From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months)
Population: All Cisplatin-eligible Randomized Participants - Sub-study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-eligible Participants for Sub-study | 7.92 Months |
| Treatment 2 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-eligible Participants for Sub-study | 7.56 Months |
p-value: 0.001895% CI: [0.59, 0.88]Log Rank
Secondary
Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study
The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It includes a global health status score, which is measured on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much. Responses are combined and converted to scores ranging from 0 to 100. A high score for global health status or health-related quality of life (HRQoL) indicates a high overall HRQoL.
Time frame: At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, and Week 120
Population: All Randomized Participants - Sub-study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Baseline | 66.6 Score on a Scale | Standard Deviation 22.7 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 24 | 4.0 Score on a Scale | Standard Deviation 25.3 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 36 | 6.4 Score on a Scale | Standard Deviation 25.1 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 48 | 7.1 Score on a Scale | Standard Deviation 24.9 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 60 | 8.1 Score on a Scale | Standard Deviation 25 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 72 | 6.6 Score on a Scale | Standard Deviation 26.5 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 84 | 9.8 Score on a Scale | Standard Deviation 26.7 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 96 | 9.0 Score on a Scale | Standard Deviation 18.2 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 108 | 7.6 Score on a Scale | Standard Deviation 13.7 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 120 | 13.9 Score on a Scale | Standard Deviation 25.5 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 4 | -0.2 Score on a Scale | Standard Deviation 22.2 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 10 | 2.9 Score on a Scale | Standard Deviation 24.2 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 16 | 1.8 Score on a Scale | Standard Deviation 23.1 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 20 | 4.3 Score on a Scale | Standard Deviation 24.6 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Baseline | 66.8 Score on a Scale | Standard Deviation 22.5 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 72 | -8.3 Score on a Scale | — |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 4 | 2.0 Score on a Scale | Standard Deviation 17.8 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 24 | -0.6 Score on a Scale | Standard Deviation 13 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 10 | 1.1 Score on a Scale | Standard Deviation 20.6 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 48 | -2.8 Score on a Scale | Standard Deviation 12.7 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 16 | -1.0 Score on a Scale | Standard Deviation 23.7 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 36 | -3.7 Score on a Scale | Standard Deviation 17.2 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study | Global Health Status - Week 20 | -0.5 Score on a Scale | Standard Deviation 22.8 |
Secondary
Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study
The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It includes a global health status score, which is measured on a 4-point Likert scale: 1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much. Responses are combined and converted to scores ranging from 0 to 100. A high score for global health status or health-related quality of life (HRQoL) indicates a high overall HRQoL.
Time frame: At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, Week 120, Week 144, Week 156, Week 168, Week 180 and Week 192
Population: All Randomized Participants - Primary Study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Baseline | 63.4 Score on a Scale | Standard Deviation 22.55 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 96 | 3.2 Score on a Scale | Standard Deviation 26.86 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 108 | 4.7 Score on a Scale | Standard Deviation 37.51 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 120 | -20.8 Score on a Scale | Standard Deviation 28.46 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 144 | -16.7 Score on a Scale | — |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 156 | -16.7 Score on a Scale | — |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 168 | 0.0 Score on a Scale | — |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 180 | -8.3 Score on a Scale | — |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 192 | -16.7 Score on a Scale | — |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 4 | -1.1 Score on a Scale | Standard Deviation 18.28 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 10 | -0.5 Score on a Scale | Standard Deviation 23.73 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 16 | 3.6 Score on a Scale | Standard Deviation 22.59 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 20 | 2.6 Score on a Scale | Standard Deviation 22.02 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 24 | 1.9 Score on a Scale | Standard Deviation 25.78 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 36 | -0.9 Score on a Scale | Standard Deviation 22.14 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 48 | 0.5 Score on a Scale | Standard Deviation 19.72 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 60 | 7.6 Score on a Scale | Standard Deviation 24.11 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 72 | 2.7 Score on a Scale | Standard Deviation 27.04 |
| Treatment 1 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 84 | 8.1 Score on a Scale | Standard Deviation 24.4 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Baseline | 59.8 Score on a Scale | Standard Deviation 25.05 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 20 | 5.1 Score on a Scale | Standard Deviation 24.44 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 4 | 2.7 Score on a Scale | Standard Deviation 23.21 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 36 | -1.7 Score on a Scale | Standard Deviation 28.81 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 10 | 3.0 Score on a Scale | Standard Deviation 23.55 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 24 | 2.5 Score on a Scale | Standard Deviation 26.19 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 16 | 3.1 Score on a Scale | Standard Deviation 24.68 |
| Treatment 2 | Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study | Global Health Status - Week 48 | 2.8 Score on a Scale | Standard Deviation 17.35 |
Secondary
Overall Survival (OS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study
This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the sub-study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer. The results are reviewed by independent experts who do not know which treatment each participant received, using standard criteria for measuring tumor response.
Time frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
Population: All PD-L1 \>= 1% Randomized Participants - Sub-study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Overall Survival (OS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study | 25.10 Months |
| Treatment 2 | Overall Survival (OS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study | 15.34 Months |
Secondary
Overall Survival (OS) in All Randomized Participants for Primary Study
This measure looks at how long all participants live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help all participants in the study live longer.
Time frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
Population: All Randomized Participants - Primary Study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Overall Survival (OS) in All Randomized Participants for Primary Study | 18.76 Months |
| Treatment 2 | Overall Survival (OS) in All Randomized Participants for Primary Study | 14.32 Months |
Secondary
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study
This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a lab test called immunohistochemistry or IHC) live without their cancer getting worse after being assigned to a treatment group in the sub-study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check.
Time frame: From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months)
Population: All PD-L1 \>= 1% Randomized Participants - Sub-study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study | 8.08 Months |
| Treatment 2 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study | 6.60 Months |
Secondary
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in All Randomized Participants for Primary Study
This measure looks at how long all participants in the primary study live without their cancer getting worse after being assigned to a treatment group. Progression-Free Survival (PFS) is defined as the time from when a participant is assigned to a treatment group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment the participant received. These experts use standard rules (called RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand whether the treatment can help participants live longer without their cancer progressing.
Time frame: From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months)
Population: All Randomized Participants - Primary Study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in All Randomized Participants for Primary Study | 5.03 Months |
| Treatment 2 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in All Randomized Participants for Primary Study | 6.01 Months |
Secondary
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-ineligible Randomized Participants for Primary Study
This measure looks at how long people who cannot receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the primary study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people unable to receive cisplatin live longer without their cancer progressing.
Time frame: From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months)
Population: All Cisplatin-ineligible Randomized Participants - Primary Study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-ineligible Randomized Participants for Primary Study | 5.29 Months |
| Treatment 2 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-ineligible Randomized Participants for Primary Study | 5.88 Months |
Secondary
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Participants for Primary Study
This measure looks at how long people with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a lab test) live without their cancer getting worse after being assigned to a treatment group in the primary study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people with PD-L1 positive tumors live longer without their cancer progressing.
Time frame: From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months)
Population: All PD-L1 \>= 1% Randomized Participants - Primary Study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Participants for Primary Study | 5.39 Months |
| Treatment 2 | Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Participants for Primary Study | 5.78 Months |