Trial Outcomes & Findings for Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer (NCT NCT03036098)

Last Updated: 2025-10-24

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

1314 participants

Primary outcome timeframe

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)

Results posted on

2025-10-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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	Treatment 2 Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study	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	Treatment 4 Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Sub-study
Pre-Treatment STARTED	349	357	304	304
Pre-Treatment COMPLETED	345	338	304	291
Pre-Treatment NOT COMPLETED	4	19	0	13
Treatment STARTED	345	325	304	288
Treatment Received Different Treatment Than Originally Assigned	0	13	0	3
Treatment COMPLETED	46	149	29	157
Treatment NOT COMPLETED	299	176	275	131

Reasons for withdrawal

Reasons for withdrawal
Measure	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	Treatment 2 Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study	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	Treatment 4 Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Sub-study
Pre-Treatment Other Reasons	1	2	0	5
Pre-Treatment Participant No Longer Meets Study Criteria	2	0	0	2
Pre-Treatment Withdrawal by Subject	1	14	0	5
Pre-Treatment Participant Request to Discontinue Study Treatment	0	3	0	1
Treatment Disease Progression	130	77	168	50
Treatment Study Drug Toxicity	95	45	26	22
Treatment Death	9	3	1	2
Treatment Adverse Event Unrelated to Study Drug	18	15	10	14
Treatment Participant Request to Discontinue Study Treatment	6	18	15	18
Treatment Withdrawal by Subject	2	9	2	4
Treatment Maximum Clinical Benefit	6	1	6	10
Treatment Poor/Non Compliance	1	2	0	1
Treatment Participant No Longer Meets Study Criteria	0	1	1	1
Treatment Administrative Reason by Sponsor	1	0	2	1
Treatment Other Reasons	31	5	21	8
Treatment Ongoing Treatment	0	0	23	0

Baseline Characteristics

Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment 1 n=349 Participants 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	Treatment 2 n=357 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study	Treatment 3 n=304 Participants 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	Treatment 4 n=304 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Sub-study	Total n=1314 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	120 Participants n=5 Participants	127 Participants n=7 Participants	150 Participants n=5 Participants	148 Participants n=4 Participants	545 Participants n=21 Participants
Age, Categorical >=65 years	229 Participants n=5 Participants	230 Participants n=7 Participants	154 Participants n=5 Participants	156 Participants n=4 Participants	769 Participants n=21 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	88 Participants n=7 Participants	68 Participants n=5 Participants	70 Participants n=4 Participants	306 Participants n=21 Participants
Sex: Female, Male Male	269 Participants n=5 Participants	269 Participants n=7 Participants	236 Participants n=5 Participants	234 Participants n=4 Participants	1008 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants	33 Participants n=4 Participants	113 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	158 Participants n=5 Participants	151 Participants n=7 Participants	118 Participants n=5 Participants	119 Participants n=4 Participants	546 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	167 Participants n=5 Participants	188 Participants n=7 Participants	148 Participants n=5 Participants	152 Participants n=4 Participants	655 Participants n=21 Participants
Race/Ethnicity, Customized White	253 Participants n=5 Participants	232 Participants n=7 Participants	211 Participants n=5 Participants	225 Participants n=4 Participants	921 Participants n=21 Participants
Race/Ethnicity, Customized Black Or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized American Indian Or Alaska Native	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Race/Ethnicity, Customized Asian	79 Participants n=5 Participants	105 Participants n=7 Participants	75 Participants n=5 Participants	63 Participants n=4 Participants	322 Participants n=21 Participants
Race/Ethnicity, Customized Other	14 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants	13 Participants n=4 Participants	60 Participants n=21 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Treatment 1 n=221 Participants 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	Treatment 2 n=224 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study	19.06 Months Interval 13.47 to 22.6	13.21 Months Interval 11.63 to 15.24

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=123 Participants 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	Treatment 2 n=127 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study	16.30 Months Interval 11.53 to 21.82	14.36 Months Interval 10.48 to 17.64

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=304 Participants 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	Treatment 2 n=304 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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 Interval 7.62 to 9.49	7.56 Months Interval 6.05 to 7.75

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=304 Participants 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	Treatment 2 n=304 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study	21.72 Months Interval 18.63 to 26.38	18.86 Months Interval 14.72 to 22.44

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=349 Participants 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	Treatment 2 n=357 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
Overall Survival (OS) in All Randomized Participants for Primary Study	18.76 Months Interval 15.05 to 21.82	14.32 Months Interval 12.22 to 15.87

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=221 Participants 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	Treatment 2 n=224 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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 Interval 3.78 to 5.95	5.88 Months Interval 5.62 to 7.59

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=123 Participants 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	Treatment 2 n=127 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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 Interval 3.75 to 7.39	5.78 Months Interval 4.8 to 6.93

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=349 Participants 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	Treatment 2 n=357 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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 Interval 3.94 to 5.98	6.01 Months Interval 5.78 to 7.52

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=349 Participants 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	Treatment 2 n=357 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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	59.8 Score on a Scale Standard Deviation 25.05
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	2.7 Score on a Scale Standard Deviation 23.21
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	3.0 Score on a Scale Standard Deviation 23.55
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	3.1 Score on a Scale Standard Deviation 24.68
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	5.1 Score on a Scale Standard Deviation 24.44
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	2.5 Score on a Scale Standard Deviation 26.19
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	-1.7 Score on a Scale Standard Deviation 28.81
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	2.8 Score on a Scale Standard Deviation 17.35
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	—
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	—
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 24.40	—
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	—
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	—
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	—
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 Standard Deviation NA Insufficient number of participants to calculate SD.	—
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 Standard Deviation NA Insufficient number of participants to calculate SD.	—
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 Standard Deviation NA Insufficient number of participants to calculate SD.	—
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 Standard Deviation NA Insufficient number of participants to calculate SD.	—
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 Standard Deviation NA Insufficient number of participants to calculate SD.	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Treatment 1 n=304 Participants 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	Treatment 2 n=304 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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	66.8 Score on a Scale Standard Deviation 22.5
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	2.0 Score on a Scale Standard Deviation 17.8
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	1.1 Score on a Scale Standard Deviation 20.6
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	-1.0 Score on a Scale Standard Deviation 23.7
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	-0.5 Score on a Scale Standard Deviation 22.8
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	-0.6 Score on a Scale Standard Deviation 13.0
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	-3.7 Score on a Scale Standard Deviation 17.2
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	7.1 Score on a Scale Standard Deviation 24.9	-2.8 Score on a Scale Standard Deviation 12.7
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 25.0	—
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	-8.3 Score on a Scale Standard Deviation NA Insufficient number of participants to calculate SD.
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	—
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	—
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	—
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	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=111 Participants 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	Treatment 2 n=110 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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 Interval 7.1 to 11.27	6.60 Months Interval 5.78 to 7.59

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment 1 n=111 Participants 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	Treatment 2 n=110 Participants Participants received Standard of Care treatment every three weeks (Q3W) for up to 6 cycles - Primary Study
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 Interval 17.28 to 35.55	15.34 Months Interval 11.7 to 24.87

Adverse Events

Treatment 1

Serious events: 264 serious events

Other events: 322 other events

Deaths: 257 deaths

Treatment 2

Serious events: 170 serious events

Other events: 309 other events

Deaths: 294 deaths

Treatment 3

Serious events: 168 serious events

Other events: 298 other events

Deaths: 172 deaths

Treatment 4

Serious events: 130 serious events

Other events: 295 other events

Deaths: 193 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER