Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Placebo

Bristol-Myers Squibb

The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.

An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove the Cancer

A Phase 3 Randomized, Double-blind, Multi-center Study of Adjuvant Nivolumab Versus Placebo in Subjects With High Risk Invasive Urothelial Carcinoma (CheckMate 274: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 274)

The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.

The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.

the time from randomization to the date of death from any cause.

the time from randomization to the date of death due to disease (urothelial cancer).

Ono Pharmaceutical Co. Ltd

All Treated Participants

All cause mortality is currently blinded at this time and will not be reported.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bristol-Myers Squibb Study Director

Disease Free Survival (DFS)

All Randomized Participants with PD-L1 expression ≥ 1%

Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population

Non-Urothelial Tract Recurrence Free Survival

Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population

Overall Survival

Overall Survival in Participants With PD-L1 Expression ≥ 1%

Disease Specific Survival

Disease Specific Survival in Participants With PD-L1 Expression ≥ 1%

Randomized

Treatment Period

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Urinary Bladder Neoplasms

Nivolumab intravenous infusion as specified

The purpose the study is to measure the effect of nivolumab (BMS-936558) in reducing tumor size in subjects with metastatic or unresectable bladder cancer.

A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer

A Phase II Single Arm Clinical Trial of Nivolumab (BMS-936558) in Subjects With Metastatic or Unresectable Urothelial Cancer Who Have Progressed or Recurred Following Treatment With a Platinum Agent

Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee

Objective Response Rate (ORR) was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells. n = Number of participants in each category

TTR is defined as the time from first dosing date to the date of the first confirmed complete response (CR) or partial response (PR), as assessed by the Blinded Independent Review Committee (BIRC). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

DOR is defined as the time from first confirmed response, complete response (CR) or partial response (PR) to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment.

PFS was defined as the time from first dosing date to the date of the first documented tumor progression, based on Blinded Independent Review Committee (BIRC) assessments or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PD-L1 expression level is defined as membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Overall Survival was defined as the time from first dosing date to the date of death. A participant who had not died was censored at last known date alive. PD-L1 expression level = membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Investigator-assessed ORR was defined as the percent of participants with a best overall response of confirmed complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD-L1 expression level = Membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Nivolumab 3 mg/kg was administered as a 60 minute IV infusion Q2W

Nivolumab 3 mg/kg

Race/Ethnicity, Customized

All treated participants. Treated participants from Japan enrolled after main enrollment period were excluded from primary efficacy analysis.

Objective Response Rate Per BIRC Assessment

PD-L1 <1%

PD-L1 >= 1%

PD-L1 <5%

PD-L1 >=5%

ORR Per BIRC Assessment by PD-L1 Expression Level

All treated participants

Progression Free Survival (PFS)

Overall Survival (OS)

Objective Response Rate (ORR) Per Investigator

TTR is defined as the time from first dosing date to the date of the first confirmed complete response (CR) or partial response (PR), as assessed by the Blinded Independent Review Committee (BIRC). Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date.

All responders-includes responders who had neither progressed nor initiated subsequent therapy at the time of analysis, and excludes responders censored prior to 12 weeks of the clinical data cutoff date (if this cutoff date is before week 48) or prior to 18 weeks of the clinical data cutoff date (if this cutoff date is after or on week 48)

Time to Response (TTR) - Extended Collection

DOR is the time from first confirmed response, complete (CR) or partial response (PR) to the date of the first tumor progression PER RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants without prior reported progression will be censored at the last evaluable tumor assessments prior to subsequent anticancer therapy. Participants who die without a reported prior progression will be considered on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date.

Duration of Response (DOR) - Extended Collection

Time to Response (TTR)

Duration of Response (DOR)

Objective Response Rate (ORR) was defined as the percent of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria). RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. BIRC= blinded independent review committee PD-L1 expression level= membranous staining in greater than or equal to 5% and greater than or equal to 1% tumor cells.

Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date."

Objective Response Rate (ORR) Per BIRC Assessment - Extended Collection

Overall Study

Digestive System Diseases

Esophageal Neoplasms

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Esophageal Cancer

Fluorouracil

Cisplatin

Ipilimumab

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

The main purpose of this study is to compare how long subjects with esophageal cancer live overall or live without disease progression after receiving nivolumab and ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin

A Study to Evaluate Efficacy in Subjects With Esophageal Cancer Treated With Nivolumab and Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin

A Randomized Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin in Subjects With Unresectable Advanced, Recurrent or Metastatic Previously Untreated Esophageal Squamous Cell Carcinoma

Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.

Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented progressive disease (PD) per Blinded Independent Central Review (BICR) or death due to any cause. Participants who die without a reported prior PD per BICR (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Participants who did not have documented PD per BICR per RECIST1.1 criteria and who did not die, will be censored at the date of the last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. Participants who did not have any on-study tumor assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported PD per BICR will be censored at the last tumor assessment on or prior to initiation of the subsequent anti-cancer therapy.

Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation as determined by BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1) or the date of subsequent anti-cancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Complete response is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to \<10 mm.

Participants will receive treatment with nivolumab 3 mg/kg as a 30-minute infusion every 2 weeks and ipilimumab as a 30-minute infusion 1 mg/kg every 6 weeks.

Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg

Participants will receive treatment with nivolumab 240 mg as a 30-minute infusion on Day 1 and Day 15, fluorouracil 800 mg/m²/day as an IV continuous infusion on Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² as a 30- to 120-minute infusion on Day 1 of 4-week cycle.

Nivolumab 240 mg + Chemotherapy

Participants will receive treatment with fluorouracil 800 mg/m²/day as an IV continuous infusion from Day 1 through Day 5 (for 5 days), and cisplatin 80 mg/m² as a 30- to 120-minute infusion on Day 1 of 4-week cycle.

Chemotherapy

Arm A: Nivolumab + Ipilimumab

Arm B: Nivolumab + Chemotherapy

Arm C: Chemotherapy

White

Black or African American

American Indian or Alaska Native

Asian Indian

Chinese

Japanese

Asian Other

Other

Hazard Ratio is Arm A: Nivolumab + Ipilimumab over Arm C: Chemotherapy.

Hazard Ratio is Arm B: Nivolumab + Chemotherapy over Arm C: Chemotherapy

All randomized PD-L1 expressing participants

Overall Survival (OS) in Participants With Tumor Cell PD-L1

Hazard Ratio is Arm A: Nivolumab + Ipilimumab over Arm C: Chemotherapy

Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1

Overall Survival (OS) in All Randomized Participants

Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR

Participants with baseline PD-L1 status < 1%

Participants with baseline PD-L1 status >= 1%

Participants with baseline PD-L1 status < 5%

Participants with baseline PD-L1 status >= 5%

Participants with baseline PD-L1 status < 10%

Participants with baseline PD-L1 status >= 10%

Participants with baseline PD-L1 status indeterminate, not evaluable, or missing

All randomized participants

All randomized PD-L1 expressing participants and all randomized participants

Objective Response Rate (ORR) as Assessed by BICR

Pre-Treatment

Treatment

Nervous System Diseases

Central Nervous System Neoplasms

The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.

A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies

Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies

A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed \> 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC).

The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.

The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy.

Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.

Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.

Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.

Progression is defined as:

* ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement
* Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids
* Any new lesion
* Clear clinical deterioration not attributable to other causes apart from the tumor
* Failure to return for evaluation as a result of death or deteriorating condition
* Clear progression of non-measurable disease

Overall survival at 12 months (OS12) is defined as the percentage of participants who are alive at 12 months, measured as the survival rate at 12 months from Kaplan-Meier product limit cumulative probability.

Progression-free survival at 6 months (PFS6) is defined as the percentage of participants who are progression free and alive at 6 months following first dose date, measured as the survival rate at 6 months from Kaplan-Meier product limit cumulative probability of progression free.

Progression is defined as:

* ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement
* Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids
* Any new lesion
* Clear clinical deterioration not attributable to other causes apart from the tumor
* Failure to return for evaluation as a result of death or deteriorating condition
* Clear progression of non-measurable disease

Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.

The number of treated participants who experienced an Adverse Event (AE) during the course of the study.

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.

The number of treated participants who experienced a Serious Adverse Event (SAE) during the course of the study.

SAE is defined as any untoward medical occurrence that, at any dose:

* Results in death
* Is life-threatening
* Requires inpatient hospitalization or causes prolongation of existing hospitalization
* Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Is an important medical event

Note: The reporting timeframe of the SAEs for this Outcome Measure (first dose to 30 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the AE section of the results form (first dose to 100 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied.

The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study.

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.

The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study.

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.

The number of treated participants who died during the course of the study.

The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study.

Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Units per Liter (U/L) Results reported in International System of Units (SI)

The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study.

Free T3 (FT3) Free T4 (FT4) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Milliunits per Liter (mlU/L) Results reported in International System of Units (SI)

Note: The reporting timeframe of the below SAEs (first dose to 100 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the Outcome Measures section of the results form (first dose to 30 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied.

Module A: nivolumab 3 mg/kg every 2 weeks.

Cohort 1: participants with newly-diagnosed DIPG, including midline glioma with H3K27M mutation.

Arm A1

Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.

Cohort 1: participants with newly-diagnosed DIPG, including midline glioma with H3K27M mutation.

Arm B1

Module A: nivolumab 3 mg/kg every 2 weeks.

Cohort 2: participants with recurrent or progressive non-brainstem HGG, regardless of mutation status, including glioblastoma.

Arm A2

Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.

Cohort 2: participants with recurrent or progressive non-brainstem HGG, regardless of mutation status, including glioblastoma.

Arm B2

Module A: nivolumab 3 mg/kg every 2 weeks.

Cohort 3: participants with relapsed or resistant medulloblastoma.

Arm A3

Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.

Cohort 3: participants with relapsed or resistant medulloblastoma.

Arm B3

Module A: nivolumab 3 mg/kg every 2 weeks.

Cohort 4: participants with relapsed or resistant ependymoma.

Arm A4

Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.

Cohort 4: participants with relapsed or resistant ependymoma.

Arm B4

Module A: nivolumab 3 mg/kg every 2 weeks.

Cohort 5: participants with other recurrent subtypes of high-grade CNS malignancy (eg, pineoblastoma, AT/RT, germ cell tumor, and others).

Arm A5

Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.

Cohort 5: participants with other recurrent subtypes of high-grade CNS malignancy (eg, pineoblastoma, AT/RT, germ cell tumor, and others).

Arm B5

Age, Customized

Arm A1, Safety Lead-in

Arms A2-A5, Safety Lead-in

Arms B2-B5, Safety Lead-in

Safety Lead-in participants: In Module A, the first 6 DLT-evaluable participants in Cohort 1 and the first 10 DLT-evaluable participants in Cohorts 2-5; in Module B, the first 10 DLT-evaluable participants.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove the Cancer	NCT02632409	Various Advance...	Nivolumab Placebo	18 Years -	Bristol-Myers Squibb
A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer	NCT02387996	Various Advance...	Nivolumab	18 Years -	Bristol-Myers Squibb
A Study to Evaluate Efficacy in Subjects With Esophageal Cancer Treated With Nivolumab and Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin	NCT03143153	Various Advance...	Nivolumab Ipilimumab Cisplatin Fluorouracil	18 Years -	Bristol-Myers Squibb
A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies	NCT03130959	Various Advance...	Nivolumab Ipilimumab	6 Months - 21 Years	Bristol-Myers Squibb
Phase I Ascending Multiple-Dose Study of BMS-986115 in Subjects With Advanced Solid Tumors	NCT01986218	Various Advance...	BMS-986115	18 Years -	Bristol-Myers Squibb
An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors	NCT02488759	Various Advance...	Nivolumab Ipilimumab Relatlimab Daratumumab	18 Years -	Bristol-Myers Squibb
A Study of Nivolumab in Participants With Metastatic or Unresectable Bladder Cancer	NCT02387996	Various Advance...	Nivolumab	18 Years -	Bristol-Myers Squibb

Spots Global Cancer Trial Database for various advanced cancer