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NCT03138512: CheckMate 914

A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney

Completed Phase 3 Results posted Last updated 18 December 2024
What this trial tests

Phase 3 trial testing nivolumab in Carcinoma, Renal Cell in 1,641 participants. Completed in 1 February 2024.

Timeline
7 July 2017
Primary endpoint
28 September 2023
1 February 2024

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment1,641
Start date7 July 2017
Primary completion28 September 2023
Estimated completion1 February 2024
Sites200 locations across Italy, Colombia, Japan, Poland, Netherlands, Russia, Belgium, Mexico

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Renal Cell. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Disease-Free Survival (DFS) by BICR - Treatment Part A and B Primary · From randomization to development of local disease recurrence, distance metastasis, or death, whichever came first (up to approximately 72 months)

Disease-Free Survival (DFS) is defined as the time from randomization to development of local disease recurrence (ie, recurrence of primary tumor in situ or occurrence of a secondary renal cell carcinoma (RCC) primary cancer), distance metastasis, or death, whichever came first per Blinded Independent Central Review (BICR) based on Kaplan-Meier estimates.

GroupValue95% CI
Treatment Part A: Nivo + IpiNANA – NA
Treatment Part A: PlaceboNA65.58 – NA
Treatment Part B: PlaceboNANA – NA
Treatment Part B: NivoNANA – NA
Overall Survival (OS) - Treatment Part A and B Secondary · From randomization to the date of death (up to approximately 72 months)

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 participants was known to be alive. Based on Kaplan-Meier estimates.

GroupValue95% CI
Treatment Part A: Nivo + IpiNANA – NA
Treatment Part A: PlaceboNANA – NA
Treatment Part B: PlaceboNANA – NA
Treatment Part B: NivoNANA – NA
Overall Survival (OS) Rate (5 Years) - Treatment Part A and B Secondary · At 5 years

Overall survival rate at 5 years is defined as the percentage of participants who are alive at 5 years.

GroupValue95% CI
Treatment Part A: Nivo + Ipi85.080.8 – 88.3
Treatment Part A: Placebo87.282.8 – 90.5
Disease-Free Survival (DFS) Per BICR in Contemporaneously Randomized Combination and Monotherapy Participants - Treatment Part B Secondary · From randomization to development of local disease recurrence, distance metastasis, or death, whichever came first (up to approximately 72 months)

Disease-Free Survival (DFS) is defined as the time from randomization to development of local disease recurrence (ie, recurrence of primary tumor in situ or occurrence of a secondary renal cell carcinoma (RCC) primary cancer), distance metastasis, or death, whichever came first per Blinded Independent Central Review (BICR) based on Kaplan-Meier estimates.

GroupValue95% CI
Treatment Part B: Nivo + IpiNA36.17 – NA
Treatment Part B: NivoNANA – NA
Overall Survival (OS) in the Contemporaneously Randomized Combination and Monotherapy Participants - Treatment Part B Secondary · From randomization to the date of death (up to approximately 72 months)

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 participants was known to be alive. Based on Kaplan-Meier estimates

GroupValue95% CI
Treatment Part B: Nivo + IpiNANA – NA
Treatment Part B: NivoNANA – NA
The Number of Participants With Adverse Events up to 30 Days After Last Dose of Study Therapy - Treatment Part A Secondary · From first dose to 30 days post last dose (up to approximately 40 weeks)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.

Any Grade AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi392
Treatment Part A: Placebo362
Grade 3-4 AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi154
Treatment Part A: Placebo44
Grade 5 AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi1
Treatment Part A: Placebo0
Any Grade Drug-Related AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi359
Treatment Part A: Placebo230
Grade 3-4 Drug-Related AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi114
Treatment Part A: Placebo8
Grade 5 Drug-Related AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi0
Treatment Part A: Placebo0
The Number of Participants With Adverse Events up to 30 Days After Last Dose of Study Therapy - Treatment Part B Secondary · From first dose to 30 days post last dose (up to approximately 40 weeks)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.

Any Grade AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi193
Treatment Part B: Placebo182
Treatment Part B: Nivo362
Grade 3-4 AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi59
Treatment Part B: Placebo31
Treatment Part B: Nivo70
Grade 5 AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi1
Treatment Part B: Placebo1
Treatment Part B: Nivo0
Any Grade Drug-Related AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi173
Treatment Part B: Placebo107
Treatment Part B: Nivo297
Grade 3-4 Drug-Related AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi41
Treatment Part B: Placebo4
Treatment Part B: Nivo36
Grade 5 Drug-Related AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi0
Treatment Part B: Placebo0
Treatment Part B: Nivo0
The Number of Participants With Adverse Events up to 100 Days After Last Dose of Study Therapy - Treatment Part A Secondary · From first dose to 100 days post last dose (up to approximately 50 weeks)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.

Any Grade AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi393
Treatment Part A: Placebo365
Grade 3-4 AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi167
Treatment Part A: Placebo52
Grade 5 AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi4
Treatment Part A: Placebo1
Any Grade Drug-Related AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi361
Treatment Part A: Placebo230
Grade 3-4 Drug-Related AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi128
Treatment Part A: Placebo9
Grade 5 Drug-Related AE
GroupValue95% CI
Treatment Part A: Nivo + Ipi2
Treatment Part A: Placebo0
The Number of Participants With Adverse Events up to 100 Days After Last Dose of Study Therapy - Treatment Part B Secondary · From first dose to 100 days post last dose (up to approximately 50 weeks)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.

Any Grade AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi196
Treatment Part B: Placebo182
Treatment Part B: Nivo367
Grade 3-4 AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi68
Treatment Part B: Placebo32
Treatment Part B: Nivo85
Grade 5 AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi5
Treatment Part B: Placebo2
Treatment Part B: Nivo2
Any Grade Drug-Related AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi175
Treatment Part B: Placebo108
Treatment Part B: Nivo300
Grade 3-4 Drug-Related AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi46
Treatment Part B: Placebo5
Treatment Part B: Nivo46
Grade 5 Drug-Related AE
GroupValue95% CI
Treatment Part B: Nivo + Ipi0
Treatment Part B: Placebo0
Treatment Part B: Nivo0
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 30 Days - Treatment Part A Secondary · From first dose to 30 days post last dose (up to approximately 40 weeks)

Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.

HEMOGLOBIN
GroupValue95% CI
Treatment Part A: Nivo + Ipi1
Treatment Part A: Placebo1
PLATELET COUNT
GroupValue95% CI
Treatment Part A: Nivo + Ipi1
Treatment Part A: Placebo0
LEUKOCYTES, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi0
Treatment Part A: Placebo0
LYMPHOCYTES (ABSOLUTE), TOTAL
GroupValue95% CI
Treatment Part A: Nivo + Ipi6
Treatment Part A: Placebo3
ABSOLUTE NEUTROPHIL COUNT
GroupValue95% CI
Treatment Part A: Nivo + Ipi2
Treatment Part A: Placebo0
ALKALINE PHOSPHATASE, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi3
Treatment Part A: Placebo0
ASPARTATE AMINOTRANSFERASE, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi14
Treatment Part A: Placebo3
ALANINE AMINOTRANSFERASE, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi16
Treatment Part A: Placebo5
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 30 Days - Treatment Part B Secondary · From first dose to 30 days post last dose (up to approximately 40 weeks)

Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.

HEMOGLOBIN
GroupValue95% CI
Treatment Part B: Nivo + Ipi0
Treatment Part B: Placebo3
Treatment Part B: Nivo0
PLATELET COUNT
GroupValue95% CI
Treatment Part B: Nivo + Ipi0
Treatment Part B: Placebo1
Treatment Part B: Nivo0
LEUKOCYTES, LOCAL LAB
GroupValue95% CI
Treatment Part B: Nivo + Ipi0
Treatment Part B: Placebo0
Treatment Part B: Nivo1
LYMPHOCYTES (ABSOLUTE), TOTAL
GroupValue95% CI
Treatment Part B: Nivo + Ipi3
Treatment Part B: Placebo1
Treatment Part B: Nivo4
ABSOLUTE NEUTROPHIL COUNT
GroupValue95% CI
Treatment Part B: Nivo + Ipi0
Treatment Part B: Placebo0
Treatment Part B: Nivo1
ALKALINE PHOSPHATASE, LOCAL LAB
GroupValue95% CI
Treatment Part B: Nivo + Ipi1
Treatment Part B: Placebo1
Treatment Part B: Nivo0
ASPARTATE AMINOTRANSFERASE, LOCAL LAB
GroupValue95% CI
Treatment Part B: Nivo + Ipi4
Treatment Part B: Placebo4
Treatment Part B: Nivo5
ALANINE AMINOTRANSFERASE, LOCAL LAB
GroupValue95% CI
Treatment Part B: Nivo + Ipi7
Treatment Part B: Placebo3
Treatment Part B: Nivo8
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 100 Days - Treatment Part A Secondary · From first dose to 100 days post last dose (up to approximately 50 weeks)

Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.

HEMOGLOBIN
GroupValue95% CI
Treatment Part A: Nivo + Ipi1
Treatment Part A: Placebo1
PLATELET COUNT
GroupValue95% CI
Treatment Part A: Nivo + Ipi1
Treatment Part A: Placebo0
LEUKOCYTES, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi0
Treatment Part A: Placebo0
LYMPHOCYTES (ABSOLUTE), TOTAL
GroupValue95% CI
Treatment Part A: Nivo + Ipi11
Treatment Part A: Placebo3
ABSOLUTE NEUTROPHIL COUNT
GroupValue95% CI
Treatment Part A: Nivo + Ipi2
Treatment Part A: Placebo0
ALKALINE PHOSPHATASE, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi5
Treatment Part A: Placebo0
ASPARTATE AMINOTRANSFERASE, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi17
Treatment Part A: Placebo3
ALANINE AMINOTRANSFERASE, LOCAL LAB
GroupValue95% CI
Treatment Part A: Nivo + Ipi20
Treatment Part A: Placebo6

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality was assessed from a participants first dose to their study completion (up to approximately 72 months) SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 50 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Part A and B: Nivo + Ipi
Serious: 196/608 (32%)
Deaths: 65/611
Treatment Part A and B: Placebo
Serious: 49/614 (8%)
Deaths: 55/619
Treatment Part B: Nivo
Serious: 56/408 (14%)
Deaths: 22/411

Serious adverse events (219 terms)

ReactionSystemTreatment Part A and B: Ni…Treatment Part A and B: Pl…Treatment Part B: Nivo
Adrenal insufficiencyEndocrine disorders
DiarrhoeaGastrointestinal disorders
Acute kidney injuryRenal and urinary disorders
HypophysitisEndocrine disorders
ColitisGastrointestinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Immune-mediated enterocolitisGastrointestinal disorders
PneumoniaInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
HypopituitarismEndocrine disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
Urinary tract infectionInfections and infestations
Type 1 diabetes mellitusMetabolism and nutrition disorders
MyocarditisCardiac disorders
PancreatitisGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Diabetes mellitusMetabolism and nutrition disorders
Diabetic ketoacidosisMetabolism and nutrition disorders
Recurrent cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HeadacheNervous system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Acute myocardial infarctionCardiac disorders
Other adverse events (33 terms — click to expand)

ReactionSystemTreatment Part A and B: Ni…Treatment Part A and B: Pl…Treatment Part B: Nivo
PruritusSkin and subcutaneous tissue disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
HypothyroidismEndocrine disorders
RashSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
HeadacheNervous system disorders
HyperthyroidismEndocrine disorders
Blood creatinine increasedInvestigations
Alanine aminotransferase increasedInvestigations
AstheniaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
Aspartate aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Adrenal insufficiencyEndocrine disorders
VomitingGastrointestinal disorders
InsomniaPsychiatric disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
HypertensionVascular disorders
Abdominal painGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HyperglycaemiaMetabolism and nutrition disorders
COVID-19Infections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Adrenal insufficiency, Diarrhoea, Acute kidney injury, Hypophysitis, Colitis, Pneumonitis, Immune-mediated enterocolitis, Pneumonia.

Data from ClinicalTrials.gov NCT03138512 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial.
    Motzer RJ, Rini BI, McDermott DF, Arén Frontera O, et al · · 2019 · cited 595× · PMID 31427204 · DOI 10.1016/s1470-2045(19)30413-9
  2. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC).
    Rini BI, Battle D, Figlin RA, George DJ, et al · · 2019 · cited 197× · PMID 31856918 · DOI 10.1186/s40425-019-0813-8
  3. Immunotherapy in Renal Cell Carcinoma: The Future Is Now.
    Deleuze A, Saout J, Dugay F, Peyronnet B, et al · · 2020 · cited 178× · PMID 32260578 · DOI 10.3390/ijms21072532
  4. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double-blind, randomised, phase 3 trial.
    Motzer RJ, Russo P, Grünwald V, Tomita Y, et al · · 2023 · cited 131× · PMID 36774933 · DOI 10.1016/s0140-6736(22)02574-0
  5. Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma.
    Sharma R, Kadife E, Myers M, Kannourakis G, et al · · 2021 · cited 120× · PMID 34099013 · DOI 10.1186/s13046-021-01961-3
  6. Dendritic Cell Cancer Therapy: Vaccinating the Right Patient at the Right Time.
    van Willigen WW, Bloemendal M, Gerritsen WR, Schreibelt G, et al · · 2018 · cited 102× · PMID 30327656 · DOI 10.3389/fimmu.2018.02265
  7. Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.
    Wei J, Li W, Zhang P, Guo F, et al · · 2024 · cited 82× · PMID 39725966 · DOI 10.1186/s12943-024-02179-5
  8. Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma.
    Kammerer-Jacquet SF, Deleuze A, Saout J, Mathieu R, et al · · 2019 · cited 64× · PMID 30987368 · DOI 10.3390/ijms20071692

Verify or expand the search:

Other trials of nivolumab

Trials testing the same drug.

Other recruiting trials for Carcinoma, Renal Cell

Currently open trials in the same condition.

Other Bristol-Myers Squibb trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03138512.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing