Trial · NCT01668784
Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)
NCT01668784, Phase 3, Completed, Bristol-Myers Squibb; results first posted 2016-04-29
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025). Trials, record NCT01668784. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01668784
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)
- NCT number
- NCT01668784
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 821 participants, actual
- Lead sponsor
- Bristol-Myers Squibb
- Conditions
- Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
- Interventions
- Nivolumab, Everolimus
- First posted
- 2012-08-20
- Last updated
- 2022-08-09
- Other registries' IDs
- eudract:2011-005132-26
- Results first posted
- 2016-04-29
Source ClinicalTrials.gov
Registered outcomes10
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Overall Survival (OS) at Primary Endpoint | Randomization until 398 deaths, up to May 2015 (approximately 30 months) | Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p \< 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria. |
| Secondary | Investigator-assessed Objective Response Rate (ORR) | from randomization up to disease progression or death (approximately up to 105 Months) | ORR is defined as Percentage of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. 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, the baseline sum diameters used as reference. Tumor assessments began at 8 weeks following randomization and continued every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or death. CIs used Clopper and Pearson. |
| Secondary | Investigator-assessed Duration of Objective Response | From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months) | Duration of objective response is defined as the time from study start date to response, CR or partial response, PR) to the date of the first documented tumor progression as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. For participants who neither progress nor die, the duration of objective response were censored at the same time they were censored for the primary definition. 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, the baseline sum diameters used as reference. Based on Kaplan-Meier Estimates. |
| Secondary | Investigator-assessed Time to Objective Response | Randomization to date of first response (approximately 105 months) | Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). 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, the baseline sum diameters used as reference. |
| Secondary | Investigator-assessed Time of Progression-free Survival (PFS) | from randomization up to disease progression or death (approximately up to 105 Months) | PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: \>=20% increase in sum of target lesion diameters and sum must show absolute increase of \>=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates. |
| Secondary | Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level | Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months) | Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H\&E process before the tumor biopsy specimen was sent for evaluation or from H\&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable. |
| Secondary | Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events | Day of first dose to 30 days post study completion (approximately 106 months) | Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. |
| Secondary | Percentage of Participants With Disease-related Symptom Progression (DRSP) | from randomization up to disease progression or death (approximately up to 105 Months) | Disease-related symptom progression rate (DRSPR)=a decrease of two points in the Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) questionnaire relative to the participant's baseline FKSI-DRS score with no later increase above this threshold observed during the course of the study. The 9 items of the FKSI-DRS were summarized into a symptom scale ranging in score from 0 to 36, with 0 being the worst possible score and 36 being the best possible score. A single measure reporting a decrease of at least 2 units was considered disease-related symptom progression only if it was the last one available for the participant. In order to consider a questionnaire received as valid, over 50% of the items were to be completed. Calculated by the Clopper-Pearson method for each treatment group. |
| Secondary | Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests | Day 1 to 30 days post study completion (approximately 106 months) | Aspartate aminotransferase, AST. Alanine aminotransaminase, ALT. Total bilirubin, tBIL. Thyroid stimulating hormone, TSH. Upper limit of normal (ULN). Units per Liter (U/L). Results reported in International System of Units (SI). |
| Secondary | Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units | Day 1 to 30 days post study completion (approximately 106 months) | Common Terminology Criteria (CTC) version 4.0 in International System of Units (SI); Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Hematology parameters=Hemoglobin (Gr 3: \< 8.0 g/dL), Platelet Count (Gr 3: 25.0 -\< 50.0\*10\^9 c/L; Gr 4: \< 25.0\*10\^9 c/L), Leukocyte Count (Gr 3: 1.0 -\< 2.0\*10\^3 c/µL; Gr4: \< 1.0\*10\^3 c/µL), Absolute Lymphocyte Count (Gr 3: 0.2 -\< 0.5\*10\^3 c/µL; Gr 4: \< 0.2\*10\^3 c/µL), Absolute Neutrophil Count (Gr 3: 0.5 - \< 1.0\*10\^3 c/µL; Gr 4: \< 0.5\*10\^3 c/µL). Liver Function parameters=Alkaline Phosphatase (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), AST (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), ALT (Gr 3: \> 5.0 - 20.0 U/L \* ULN; Gr 4: \> 20.0 U/L \* ULN), tBIL (Gr 3: \> 3.0 - 10.0 mg/dL \* ULN; Gr 4: \> 10.0 mg/dL \* ULN). Renal parameter=Creatinine (Grade: Gr3: \> 3.0 - 6.0 mg/dL \*ULN; Gr4: \> 6.0 mg/dL \*ULN). Cells per microliter (c/µL). Cells per Liter (c/L). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL). |
Source ClinicalTrials.gov
Outcomes11
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Overall Survival (OS) at Primary Endpoint | Randomization until 398 deaths, up to May 2015 (approximately 30 months) | All randomized participants; any participants that was randomized to any treatment group in the study. | months | MEDIAN |
| SECONDARY | Investigator-assessed Objective Response Rate (ORR) | from randomization up to disease progression or death (approximately up to 105 Months) | All randomized participants; any participants that was randomized to any treatment group in the study. | percentage of participants | NUMBER |
| SECONDARY | Investigator-assessed Duration of Objective Response | From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months) | All randomized participants with a response; any participants that were randomized to any treatment group in the study and that had a response. | months | MEDIAN |
| SECONDARY | Investigator-assessed Time to Objective Response | Randomization to date of first response (approximately 105 months) | All randomized participants with a response; any participants that was randomized to any treatment group in the study and that had a response. | months | MEDIAN |
| SECONDARY | Investigator-assessed Time of Progression-free Survival (PFS) | from randomization up to disease progression or death (approximately up to 105 Months) | All randomized participants; any participants that was randomized to any treatment group in the study. | months | MEDIAN |
| SECONDARY | Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level | Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months) | PD-L1 quantifiable participants; All randomized participants with quantifiable PD-L1 expression at baseline | months | MEDIAN |
| SECONDARY | Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events | Day of first dose to 30 days post study completion (approximately 106 months) | All treated participants; all participants who received at least one dose of nivolumab or everolimus | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Percentage of Participants With Disease-related Symptom Progression (DRSP) | from randomization up to disease progression or death (approximately up to 105 Months) | All randomized participants; any participants that was randomized to any treatment group in the study. | percentage of participants | NUMBER |
| SECONDARY | Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests | Day 1 to 30 days post study completion (approximately 106 months) | To all treated participants with evaluable measurements | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units | Day 1 to 30 days post study completion (approximately 106 months) | To all treated participants with evaluable measurements | Participants | COUNT_OF_PARTICIPANTS |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 outcomesResults by group108
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Overall Survival (OS) at Primary Endpoint | Nivolumab | 25.00 | 95% Confidence Interval 21.75 to NA | months | |
| Overall Survival (OS) at Primary Endpoint | Everolimus | 19.55 | 95% Confidence Interval 17.64 to 23.06 | months | |
| Investigator-assessed Objective Response Rate (ORR) | Nivolumab | 25.9 | 95% Confidence Interval 21.7 to 30.4 | percentage of participants | |
| Investigator-assessed Objective Response Rate (ORR) | Everolimus | 6.1 | 95% Confidence Interval 4.0 to 8.8 | percentage of participants | |
| Investigator-assessed Duration of Objective Response | Nivolumab | 13.11 | 95% Confidence Interval 9.26 to 19.75 | months | |
| Investigator-assessed Duration of Objective Response | Everolimus | 10.18 | 95% Confidence Interval 5.39 to 18.73 | months | |
| Investigator-assessed Time to Objective Response | Nivolumab | 3.55 | Full Range 1.4 to 24.8 | months | |
| Investigator-assessed Time to Objective Response | Everolimus | 3.71 | Full Range 1.5 to 68.9 | months | |
| Investigator-assessed Time of Progression-free Survival (PFS) | Nivolumab | 4.21 | 95% Confidence Interval 3.68 to 5.36 | months | |
| Investigator-assessed Time of Progression-free Survival (PFS) | Everolimus | 4.50 | 95% Confidence Interval 3.71 to 5.52 | months |
1 to 10 of 108Source ClinicalTrials.gov
See all 108 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Randomized (Pre-treatment) | STARTED | Nivolumab | 410 | |
| Randomized (Pre-treatment) | STARTED | Everolimus | 411 | |
| Randomized (Pre-treatment) | COMPLETED | Nivolumab | 406 | |
| Randomized (Pre-treatment) | COMPLETED | Everolimus | 397 | |
| Randomized (Pre-treatment) | NOT COMPLETED | Nivolumab | 4 | |
| Randomized (Pre-treatment) | NOT COMPLETED | Everolimus | 14 | |
| Treatment Period | STARTED | Nivolumab | 406 | |
| Treatment Period | STARTED | Everolimus | 397 | |
| Treatment Period | COMPLETED | Nivolumab | 0 | |
| Treatment Period | COMPLETED | Everolimus | 0 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events772
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | NIVOLUMAB | 93 | 406 | |
| other | Anaemia | Blood and lymphatic system disorders | EVEROLIMUS | 149 | 397 | |
| other | Hypothyroidism | Endocrine disorders | NIVOLUMAB | 39 | 406 | |
| other | Hypothyroidism | Endocrine disorders | EVEROLIMUS | 15 | 397 | |
| other | Abdominal pain | Gastrointestinal disorders | NIVOLUMAB | 46 | 406 | |
| other | Abdominal pain | Gastrointestinal disorders | EVEROLIMUS | 44 | 397 | |
| other | Abdominal pain upper | Gastrointestinal disorders | NIVOLUMAB | 27 | 406 | |
| other | Abdominal pain upper | Gastrointestinal disorders | EVEROLIMUS | 22 | 397 | |
| other | Constipation | Gastrointestinal disorders | NIVOLUMAB | 110 | 406 | |
| other | Constipation | Gastrointestinal disorders | EVEROLIMUS | 93 | 397 |
1 to 10 of 772Source ClinicalTrials.gov
See all 772 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | NIVOLUMAB | 324 | 406 |
| Total, all-cause mortality | EVEROLIMUS | 342 | 397 |
| Total, other adverse events | NIVOLUMAB | 392 | 406 |
| Total, other adverse events | EVEROLIMUS | 379 | 397 |
| Total, serious adverse events | NIVOLUMAB | 248 | 406 |
| Total, serious adverse events | EVEROLIMUS | 243 | 397 |
Source ClinicalTrials.gov
Papers8
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| NIVOLUMAB vs EVEROLIMUS: deaths from any cause | Trial comparisons |
| NIVOLUMAB vs EVEROLIMUS: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01668784
GET https://conductscience.org/api/trials/v1/NCT01668784/results?page=2