NCT03036098 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study

→

outcome · POSTED

Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study

→

outcome · POSTED

Overall Survival (OS) in All Randomized Participants for Primary Study

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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/exclusion criteria apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Biological: Nivolumab
Biological: Ipilimumab
label
Arm A: Investigational immunotherapy
type
EXPERIMENTAL
intervention Names
Drug: Gemcitabine
Drug: Cisplatin
Drug: Carboplatin
label
Arm B: Standard of care chemotherapy
type
ACTIVE_COMPARATOR
intervention Names
Biological: Nivolumab
Drug: Gemcitabine
Drug: Cisplatin
label
Arm C: Investigational immunotherapy
type
EXPERIMENTAL
intervention Names
Drug: Gemcitabine
Drug: Cisplatin
label
Arm D: Standard of care chemotherapy
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A: Investigational immunotherapy
Arm C: Investigational immunotherapy
description
Specified Dose on Specified Days
name
Nivolumab
other Names
BMS-936558
Opdivo
type
BIOLOGICAL
arm Group Labels
Arm A: Investigational immunotherapy
description
Specified Dose on Specified Days
name
Ipilimumab
other Names
BMS-734016
Yervoy
type
BIOLOGICAL
arm Group Labels
Arm B: Standard of care chemotherapy
Arm C: Investigational immunotherapy
Arm D: Standard of care chemotherapy
description
Specified Dose on Specified Days
name
Gemcitabine
type
DRUG
arm Group Labels
Arm B: Standard of care chemotherapy
Arm C: Investigational immunotherapy
Arm D: Standard of care chemotherapy
description
Specified Dose on Specified Days
name
Cisplatin
type
DRUG
arm Group Labels
Arm B: Standard of care chemotherapy
description
Specified Dose on Specified Days
name
Carboplatin
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1314
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study
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)
description
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.
measure
Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study
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)
description
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.
measure
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
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)
description
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.
measure
Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study
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)

secondary Outcomes

description
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.
measure
Overall Survival (OS) in All Randomized Participants for Primary Study
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)
description
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.
measure
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
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)
description
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.
measure
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
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)
description
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.
measure
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
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)
description
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.
measure
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
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
description
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.
measure
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
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
description
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.
measure
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
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)
description
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.
measure
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
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)

Full study description

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.

Source references

references

citation
Tomita Y, Ye DW, Fujii A, Takeuchi N. Nivolumab plus gemcitabine-cisplatin for previously untreated unresectable or metastatic urothelial carcinoma: an Asian subgroup analysis from the global phase 3 CheckMate 901 trial. Urol Oncol. 2025 Dec;43(12):696.e9-696.e16. doi: 10.1016/j.urolonc.2025.08.022. Epub 2025 Sep 26.
pmid
41015742
type
DERIVED
citation
van der Heijden MS, Sonpavde G, Powles T, Necchi A, Burotto M, Schenker M, Sade JP, Bamias A, Beuzeboc P, Bedke J, Oldenburg J, Chatta G, Urun Y, Ye D, He Z, Valderrama BP, Ku JH, Tomita Y, Filian J, Wang L, Purcea D, Patel MY, Nasroulah F, Galsky MD; CheckMate 901 Trial Investigators. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023 Nov 9;389(19):1778-1789. doi: 10.1056/NEJMoa2309863. Epub 2023 Oct 22.
pmid
37870949
type
DERIVED