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NCT02982954: CHECKMATE 920

A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer

Completed Phase 4 Results posted Last updated 1 November 2022
What this trial tests

Phase 4 trial testing Nivolumab in Renal Cell Carcinoma in 211 participants. Completed in 6 October 2021.

Timeline
16 January 2017
Primary endpoint
11 May 2020
6 October 2021

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment211
Start date16 January 2017
Primary completion11 May 2020
Estimated completion6 October 2021
Sites61 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Renal Cell Carcinoma. 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.

Number of Participants With High Grade (Grade 3-4) Immune Mediated Adverse Events (IMAEs) Primary · Approximately 39 Months

Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity

Pneumonitis
GroupValue95% CI
Cohort 11
Cohort 20
Cohort 30
Cohort 40
Diarrhoea/Colitis
GroupValue95% CI
Cohort 18
Cohort 24
Cohort 32
Cohort 40
Hepatitis
GroupValue95% CI
Cohort 13
Cohort 21
Cohort 31
Cohort 41
Nephritis and Renal Dysfunction
GroupValue95% CI
Cohort 10
Cohort 22
Cohort 30
Cohort 40
Rash
GroupValue95% CI
Cohort 17
Cohort 23
Cohort 31
Cohort 40
Hypersensitivity
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Adrenal Insufficiency
GroupValue95% CI
Cohort 13
Cohort 21
Cohort 30
Cohort 41
Hypothyroidism and Thyroiditis
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 41
Number of Participants With High Grade (Grade 5) Immune Mediated Adverse Events (IMAEs) Primary · Approximately 39 Months

Number of participants with IMAEs in the following categories: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity

Pneumonitis
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Diarrhoea/Colitis
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Hepatitis
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Nephritis and Renal Dysfunction
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Rash
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Hypersensitivity
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Adrenal Insufficiency
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Hypothyroidism and Thyroiditis
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Time to Onset of Grade 3-5 Immune Mediated Adverse Events (IMAEs) Secondary · From first dose to the earliest IMAE (grade 3-5) event onset date (up to approximately 116 weeks)

Time to onset is defined as the duration of time in weeks from the first dosing to the immune modulating adverse event onset date. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the

Pneumonitis
GroupValue95% CI
Cohort 112.712.7 – 12.7
Diarrhoea/Colitis
GroupValue95% CI
Cohort 121.791.7 – 115.7
Cohort 210.434.4 – 20.1
Cohort 311.010.1 – 11.9
Hepatitis
GroupValue95% CI
Cohort 18.432.0 – 82.1
Cohort 29.49.4 – 9.4
Cohort 311.611.6 – 11.6
Cohort 410.110.1 – 10.1
Nephritis and Renal Dysfunction
GroupValue95% CI
Cohort 29.431.4 – 17.4
Rash
GroupValue95% CI
Cohort 14.001.1 – 80.4
Cohort 26.142.3 – 13.7
Cohort 38.38.3 – 8.3
Immune Mediated Arthritis
GroupValue95% CI
Cohort 238.938.9 – 38.9
Time to Resolution of Grade 3-5 Immune Mediated Adverse Events (IMAEs) Secondary · From the IMAE onset date to the IMAE end date, up to approximately 194 weeks

Time to resolution is defined as the longest time from IMAE onset date to complete resolution or improvement to the grade at baseline experienced by the participant (the IMAE end date). Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following

Pneumonitis
GroupValue95% CI
Cohort 10.90.9 – 0.9
Diarrhoea/Colitis
GroupValue95% CI
Cohort 12.710.7 – 193.9
Cohort 25.930.9 – 16.9
Cohort 31.141.1 – 4.9
Hepatitis
GroupValue95% CI
Cohort 1NA7.9 – 144.9
Cohort 2NA14.9 – 18.3
Cohort 33.003.0 – 3.0
Cohort 42.12.1 – 2.1
Nephritis and Renal Dysfunction
GroupValue95% CI
Cohort 27.791.1 – 14.4
Rash
GroupValue95% CI
Cohort 126.865.3 – 181.6
Cohort 28.003.1 – 69.9
Cohort 35.35.3 – 5.3
Adrenal Insufficiency
GroupValue95% CI
Cohort 1NA0.4 – 170.0
Cohort 46.06.0 – 6.0
Diabetes Mellitus
GroupValue95% CI
Cohort 31.11.1 – 1.1
Number of Participants Who Received Immune Modulating Medication for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) Secondary · From first dose up to 100 days post last dose (up to approximately 29 months)

The number of participants who received immune modulating medication for participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear al

Pneumonitis
GroupValue95% CI
Cohort 11
Cohort 20
Cohort 30
Cohort 40
Diarrhoea/Colitis
GroupValue95% CI
Cohort 18
Cohort 24
Cohort 32
Cohort 40
Hepatitis
GroupValue95% CI
Cohort 13
Cohort 21
Cohort 31
Cohort 41
Nephritis and Renal Dysfunction
GroupValue95% CI
Cohort 10
Cohort 22
Cohort 30
Cohort 40
Rash
GroupValue95% CI
Cohort 17
Cohort 23
Cohort 31
Cohort 40
Hypersensitivity
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 40
Adrenal Insufficiency
GroupValue95% CI
Cohort 13
Cohort 21
Cohort 30
Cohort 41
Hypothyroidism/Thyroiditis
GroupValue95% CI
Cohort 10
Cohort 20
Cohort 30
Cohort 41
Number of Participants Who Received Hormone Replacement Therapy for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) Secondary · From first dose up to 100 days post last dose (up to approximately 29 months)

The number of participants who received Hormone Replacement Therapy for experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causality (3) with no clear alternate etiolo

Pneumonitis
GroupValue95% CI
Cohort 11
Cohort 20
Cohort 30
Cohort 40
Diarrhoea/Colitis
GroupValue95% CI
Cohort 18
Cohort 23
Cohort 32
Cohort 40
Hepatitis
GroupValue95% CI
Cohort 13
Cohort 21
Cohort 31
Cohort 41
Nephritis and Renal Dysfunction
GroupValue95% CI
Cohort 10
Cohort 22
Cohort 30
Cohort 40
Rash
GroupValue95% CI
Cohort 17
Cohort 23
Cohort 31
Cohort 40
Adrenal Insufficiency
GroupValue95% CI
Cohort 12
Cohort 21
Cohort 30
Cohort 41
Number of Participants Who Received ≥ 40mg of Prednisone for High Grade (Grades 3-5) Immune Mediated Adverse Events (IMAEs) Secondary · From first dose up to 100 days post last dose (up to approximately 29 months)

The number of participants who received ≥ 40mg of prednisone for high grade (grades 3-5) IMAEs. Participants experiencing all high grade (CTCAE v4 Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) in the following categories will be included: Skin, Endocrine, Gastrointestinal, Hepatic, Renal, Pulmonary and Hypersensitivity. IMAEs are specific events (or groups of preferred terms describing specific events) considered as potential immune-mediated events by investigator, that meet the following definition: (1) those occurring within 100 days of the last dose (2) regardless of causali

GroupValue95% CI
Cohort 119
Cohort 29
Cohort 35
Cohort 42
Median Progression Free Survival (PFS) Secondary · From first dose to the date of the first documented progressive disease, up to approximately 12 months

PFS is defined as the time from first dose to the date of the first documented progressive disease (PD) as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause whichever occur first. Progressive disease is defined as progression of existing non-target lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. T

GroupValue95% CI
Cohort 14.83.0 – 8.4
Cohort 23.72.7 – 4.6
Cohort 38.52.9 – 12.0
Cohort 43.62.5 – 8.7
Objective Response Rate (ORR) Secondary · From first dose up to the date of objectively documented progression or the date of subsequent therapy, whichever occurs first (up to approximately 26 months)

ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target les

GroupValue95% CI
Cohort 135.425.9 – 45.8
Cohort 221.710.9 – 36.4
Cohort 330.814.3 – 51.8
Cohort 433.313.3 – 59.0
Time to Response Rate (TRR) Secondary · From the date of first dose to first documented CR or PR, up to approximately 15 months

TTR is defined as the median percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable participants. Best overall response is defined as the best response recorded from the start of the study treatment until the end of treatment. The participant's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of tar

GroupValue95% CI
Cohort 12.82.5 – 14.6
Cohort 22.82.1 – 4.5
Cohort 32.82.4 – 3.0
Cohort 44.52.5 – 12.1
Duration of Response (DOR) Secondary · From first confirmed response to the date of the first documented tumor progression or death, up to approximately 48 months

DOR is defined as the time between the date of first confirmed response to the date of the first documented tumor progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, whichever occurs first. DOR will be computed for participants who achieve partial response (PR) or complete response (CR) only. 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. Complete response is defined as the disappearance of all lesions and normalization of tumor marker level. All

GroupValue95% CI
Cohort 111.017.10 – NA
Cohort 237.6810.87 – NA
Cohort 316.513.88 – 47.87
Cohort 419.486.28 – 20.57

Adverse events — posted to ClinicalTrials.gov

Time frame: SAEs and NSAEs: From first dose to 100 days post last dose (up to approximately 29 months). Participants were assessed for All-cause mortality from their first dose to study completion (up to approximately 56 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1
Serious: 63/106 (59%)
Deaths: 55/106
Cohort 2
Serious: 29/52 (56%)
Deaths: 29/52
Cohort 3
Serious: 14/28 (50%)
Deaths: 15/28
Cohort 4
Serious: 17/25 (68%)
Deaths: 20/25

Serious adverse events (131 terms)

ReactionSystemCohort 1Cohort 2Cohort 3Cohort 4
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
ColitisGastrointestinal disorders
PneumoniaInfections and infestations
Atrial fibrillationCardiac disorders
Adrenal insufficiencyEndocrine disorders
DiarrhoeaGastrointestinal disorders
SepsisInfections and infestations
DehydrationMetabolism and nutrition disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Acute myocardial infarctionCardiac disorders
NauseaGastrointestinal disorders
PancreatitisGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Urinary tract infectionInfections and infestations
Blood creatinine increasedInvestigations
Hepatic enzyme increasedInvestigations
Diabetic ketoacidosisMetabolism and nutrition disorders
HypercalcaemiaMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
SyncopeNervous system disorders
Mental status changesPsychiatric disorders
Acute kidney injuryRenal and urinary disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (108 terms — click to expand)

ReactionSystemCohort 1Cohort 2Cohort 3Cohort 4
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
Lipase increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Blood creatinine increasedInvestigations
InsomniaPsychiatric disorders
DizzinessNervous system disorders
HypothyroidismEndocrine disorders
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
Amylase increasedInvestigations
DehydrationMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Weight decreasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Rash pruriticSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
Upper respiratory tract infectionInfections and infestations
HypoalbuminaemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Dry mouthGastrointestinal disorders
ChillsGeneral disorders

Most-reported serious reactions: Malignant neoplasm progression, Colitis, Pneumonia, Atrial fibrillation, Adrenal insufficiency, Diarrhoea, Sepsis, Dehydration.

Data from ClinicalTrials.gov NCT02982954 adverse events section.

Sponsor's own description

To investigate the safety of Nivolumab in combination with Ipilimumab in subjects with previously untreated advanced or metastatic Renal Cell Cancer.

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. Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial.
    Tykodi SS, Gordan LN, Alter RS, Arrowsmith E, et al · · 2022 · cited 105× · PMID 35210307 · DOI 10.1136/jitc-2021-003844
  3. Updates on Immunotherapy and Immune Landscape in Renal Clear Cell Carcinoma.
    Kim MC, Jin Z, Kolb R, Borcherding N, et al · · 2021 · cited 59× · PMID 34831009 · DOI 10.3390/cancers13225856
  4. Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course.
    Jiang M, Hu Y, Lin G, Chen C. · · 2022 · cited 36× · PMID 35795044 · DOI 10.3389/fonc.2022.906251
  5. Safety and efficacy of nivolumab plus ipilimumab in patients with advanced renal cell carcinoma with brain metastases: CheckMate 920.
    Emamekhoo H, Olsen MR, Carthon BC, Drakaki A, et al · · 2022 · cited 36× · PMID 34784056 · DOI 10.1002/cncr.34016
  6. Ipilimumab and Nivolumab as First-Line Treatment of Patients with Renal Cell Carcinoma: The Evidence to Date.
    Sheng IY, Ornstein MC. · · 2020 · cited 35× · PMID 32606975 · DOI 10.2147/cmar.s202017
  7. Unclassified renal cell carcinoma: diagnostic difficulties and treatment modalities.
    Sirohi D, Smith SC, Agarwal N, Maughan BL. · · 2018 · cited 29× · PMID 30510921 · DOI 10.2147/rru.s154932
  8. Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials.
    Johnson CB, Win SY. · · 2018 · cited 26× · PMID 29632719 · DOI 10.1080/2162402x.2017.1408744

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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/NCT02982954.

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