---
title: Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)
nct_id: NCT01668784
overall_status: COMPLETED
phase: PHASE3
sponsor: Bristol-Myers Squibb
study_type: INTERVENTIONAL
primary_condition: Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Norway, Poland, Romania, Russia, Spain, Sweden, United Kingdom
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT01668784.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT01668784"
ct_last_update_post_date: 2022-08-09
last_seen_at: "2026-05-12T07:29:01.285Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

**Official Title:** A Randomized, Open-Label, Phase 3 Study of Nivolumab (BMS-936558) vs. Everolimus in Subjects With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy

**NCT ID:** [NCT01668784](https://clinicaltrials.gov/study/NCT01668784)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE3
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 821
- **Lead Sponsor:** Bristol-Myers Squibb
- **Collaborators:** Ono Pharmaceutical Co., Ltd.
- **Conditions:** Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
- **Start Date:** 2012-10-09
- **Completion Date:** 2021-07-19
- **CT.gov Last Update:** 2022-08-09

## Brief Summary

The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of Nivolumab vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
Inclusion Criteria:

* Men \& women ≥18 years of age
* Histologic confirmation of renal cell carcinoma (RCC) with clear-cell component
* Advanced/metastatic RCC
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
* Received 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic setting
* No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting, and evidence of progression on or after last treatment regimen received and within 6 months of enrollment
* Karnofsky Performance Score ≥70%

Exclusion Criteria:

* Any Central Nervous System (CNS) metastases or history of CNS metastases
* Prior therapy with an Mammalian target of rapamycin (mTOR) inhibitor
* Any active known or suspected autoimmune disease
* Uncontrolled adrenal insufficiency
* Active chronic liver disease
* Prior malignancy active within past 3 years, except for locally curable cancers

Other protocol-defined inclusion/exclusion criteria apply
```

## Arms

- **Arm 1: Nivolumab** (EXPERIMENTAL) — Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
- **Arm 2: Everolimus** (ACTIVE_COMPARATOR) — Everolimus 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

## Interventions

- **Nivolumab** (BIOLOGICAL)
- **Everolimus** (DRUG)

## Primary Outcomes

- **Overall Survival (OS) at Primary Endpoint** _(time frame: 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 Outcomes

- **Investigator-assessed Objective Response Rate (ORR)** _(time frame: from randomization up to disease progression or death (approximately up to 105 Months))_
- **Investigator-assessed Duration of Objective Response** _(time frame: From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months))_
- **Investigator-assessed Time to Objective Response** _(time frame: Randomization to date of first response (approximately 105 months))_
- **Investigator-assessed Time of Progression-free Survival (PFS)** _(time frame: from randomization up to disease progression or death (approximately up to 105 Months))_
- **Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level** _(time frame: Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months))_
- **Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events** _(time frame: Day of first dose to 30 days post study completion (approximately 106 months))_
- **Percentage of Participants With Disease-related Symptom Progression (DRSP)** _(time frame: from randomization up to disease progression or death (approximately up to 105 Months))_
- **Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests** _(time frame: Day 1 to 30 days post study completion (approximately 106 months))_
- **Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units** _(time frame: Day 1 to 30 days post study completion (approximately 106 months))_

## Locations (168)

- Local Institution - 0182, Fayetteville, Arkansas, United States
- UCSD Moores Cancer Center, La Jolla, California, United States
- Local Institution - 0024, Los Angeles, California, United States
- University Of Southern California, Los Angeles, California, United States
- Cedars Sinai Medical Center, Los Angeles, California, United States
- Ucsf Helen Diller Family Comprehensive Cancer Center, San Francisco, California, United States
- Stanford Cancer Institute, Stanford, California, United States
- University Of Colorado, Aurora, Colorado, United States
- Georgetown University Medical Center, Washington D.C., District of Columbia, United States
- Local Institution - 0027, Washington D.C., District of Columbia, United States
- H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States
- Winship Cancer Institute., Atlanta, Georgia, United States
- Northwestern University, Chicago, Illinois, United States
- Loyola University Chicago, Maywood, Illinois, United States
- Indiana University Simon Cancer Center, Indianapolis, Indiana, United States
- University Of Iowa Hospitals And Clinics, Iowa City, Iowa, United States
- Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins, Baltimore, Maryland, United States
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- University Of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, United States
- Karmanos Cancer Institute, Detroit, Michigan, United States
- Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
- Roswell Park Cancer Institute, Buffalo, New York, United States
- Memorial Sloan Kettering Nassau, New York, New York, United States
- Weill Cornell Medical College, New York, New York, United States
- Levine Cancer Institute, Charlotte, North Carolina, United States
- Duke University Medical Center, Durham, North Carolina, United States
- The Ohio State University, Columbus, Ohio, United States
- Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States
- Temple University Hospital, Philadelphia, Pennsylvania, United States
- Medical University Of South Carolina, Charleston, South Carolina, United States
- St Francis Hospital, Greenville, South Carolina, United States
- Tennessee Oncology, PLLC, Nashville, Tennessee, United States
- Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Ut Southwestern Medical Center, Dallas, Texas, United States
- Local Institution - 0139, Houston, Texas, United States
- CTRC at UTHSC San Antonio, San Antonio, Texas, United States
- Local Institution - 0076, Richmond, Virginia, United States
- Local Institution - 0009, Seattle, Washington, United States
- University Of Washington, Seattle, Washington, United States
- COIBA, Berazategui, Buenos Aires, Argentina
- Local Institution, Capital Federal, Buenos Aires, Argentina
- Centro Para La Atencion Integral Del Paciente Oncologico, San Miguel de Tucumán, Tucumán Province, Argentina
- Local Institution, Buenos Aires, Argentina
- Local Institution, Buenos Aires, Argentina
- Instituto Oncologico De Cordoba, Córdoba, Argentina
- Local Institution - 0095, Westmead, New South Wales, Australia
- Local Institution, Woodville South, South Australia, Australia
- Local Institution, Box Hill, Victoria, Australia
- Local Institution, Clayton, Victoria, Australia
- Local Institution, Melbourne, Victoria, Australia
- Local Institution, Linz, Austria
- Local Institution, Vienna, Austria
- Local Institution, Vienna, Austria
- Local Institution, Brussels, Belgium
- Local Institution, Brussels, Belgium
- Local Institution, Ghent, Belgium
- Local Institution, Leuven, Belgium
- Local Institution - 0125, Ijuí, Rio Grande do Sul, Brazil
- Local Institution - 0124, São Paulo, Brazil
- Local Institution, São Paulo, Brazil
- Tom Baker Cancer Centre, Calgary, Alberta, Canada
- Cross Cancer Institute, Edmonton, Alberta, Canada
- BC Cancer Agency - Vancouver Centre, Vancouver, British Columbia, Canada
- Centre D'Oncologie Dr-Leon-Richard, Moncton, New Brunswick, Canada
- QEII Health Sciences Centre, Halfax, Nova Scotia, Canada
- Local Institution - 0143, Oshawa, Ontario, Canada
- Princess Margaret Hospital, Toronto, Ontario, Canada
- Chum, Hopital Notre-Dame, Montreal, Quebec, Canada
- Local Institution - 0145, Montreal, Canada
- Local Institution, Hradec Králové, Czechia
- Local Institution, Olomouc, Czechia
- Local Institution, Prague, Czechia
- Local Institution, Aarhus N, Denmark
- Local Institution, Herlev, Denmark
- Local Institution - 0137, Odense, Denmark
- Local Institution, Helsinki, Finland
- Local Institution - 0006, Vandœuvre-lès-Nancy, Lorraine, France
- Local Institution - 0008, Bordeaux, France
- Local Institution, Bordeaux, France
- Local Institution - 0007, Lyon, France
- Local Institution, Lyon, France
- Local Institution - 0004, Marseille, France
- Local Institution, Marseille, France
- Local Institution - 0118, Paris, France
- Local Institution - 0003, Poitiers, France
- Local Institution, Poitiers, France
- Local Institution - 0005, Saint-Herblain, France
- Local Institution, Saint-Herblain, France
- Local Institution - 0012, Toulouse, France
- Local Institution, Toulouse, France
- Local Institution, Vandœuvre-lès-Nancy, France
- Local Institution - 0002, Villejuif, France
- Local Institution, Villejuif, France
- Local Institution, Aachen, Germany
- Local Institution, Dresden, Germany
- Local Institution, Erlangen, Germany
- Local Institution, Essen, Germany
- Local Institution, Hanover, Germany
- Local Institution - 0126, Heidelberg, Germany
- Local Institution, Munich, Germany
- Local Institution, Tübingen, Germany
- Alexandra General Hospital Of Athens, Athens, Greece
- Euromedica General Clinic of Thessaloniki, Thessaloniki, Greece
- Local Institution, Tallaght, Dublin, Ireland
- Local Institution - 0087, Dublin, Ireland
- Local Institution, Dublin, Ireland
- Local Institution, Haifa, Israel
- Local Institution - 0148, Petah Tikva, Israel
- Local Institution, Ramat Gan, Israel
- Local Institution, Tel Aviv, Israel
- Local Institution, Arezzo, Italy
- Local Institution, Meldola (fc), Italy
- Local Institution - 0082, Milan, Italy
- Local Institution, Rimini, Italy
- Local Institution, Roma, Italy
- Local Institution, Roma, Italy
- Local Institution - 0102, Rozzano, Italy
- Local Institution, Siena, Italy
- Local Institution, Terni, Italy
- Local Institution, Akita, Akita, Japan
- Local Institution, Chiba, Chiba, Japan
- Local Institution, Higashiku, Fukuoka, Japan
- Local Institution, Sapporo, Hokkaido, Japan
- Local Institution, Sapporo, Hokkaido, Japan
- Local Institution, Morioka, Iwate, Japan
- Local Institution, Yokohama, Kanagawa, Japan
- Local Institution, Kyoto, Kyoto, Japan
- Local Institution, Osaka-sayama-shi, Osaka, Japan
- Local Institution - 0169, Suita, Osaka, Japan
- Local Institution - 0167, Hamamatsu, Shizuoka, Japan
- Local Institution, Tokushima, Tokushima, Japan
- Local Institution, Yamagata, Yamagata, Japan
- Local Institution, Kobe-city, Hyogo, Japan
- Local Institution, Kumamoto, Japan
- Local Institution, Tokyo, Japan
- Local Institution, Tokyo, Japan
- Local Institution, Tokyo, Japan
- Local Institution, Tokyo, Japan
- Local Institution, Tokyo, Japan
- Local Institution, Tokyo, Japan
- Local Institution, Bergen, Norway
- Local Institution, Lorenskog, Norway
- Local Institution, Gdansk, Poland
- Local Institution, Lodz, Poland
- Local Institution, Poznan, Poland
- Local Institution, Rybnik, Poland
- Local Institution, Warsaw, Poland
- Local Institution, Wroclaw, Poland
- Local Institution, Bucharest, Romania
- Local Institution, Craiova, Romania
- Local Institution, Iași, Romania
- Local Institution, Timișoara, Romania
- Local Institution, Moscow, Russia
- Local Institution, Moscow, Russia
- Local Institution, Saint Petersburg, Russia
- Local Institution, Pamplona, Navarre, Spain
- Local Institution, Barcelona, Spain
- Local Institution - 0064, L'Hospitalet de Llobregat, Spain
- Local Institution, Madrid, Spain
- Local Institution, Madrid, Spain
- Local Institution, Madrid, Spain
- Local Institution, Gothenberg, Sweden
- Local Institution, Solna, Sweden
- Local Institution, Cambridge, Cambridgeshire, United Kingdom
- Local Institution - 0048, Swansea, Carmarthenshire, United Kingdom
- Local Institution, Swansea, Carmarthenshire, United Kingdom
- Local Institution, London, Greater London, United Kingdom
- Local Institution, London, Greater London, United Kingdom

## Recent Field Changes (last 30 days)

- `locations.local institution|london|greater london|united kingdom` — added _(2026-05-12)_
- `locations.local institution|swansea|carmarthenshire|united kingdom` — added _(2026-05-12)_
- `locations.local institution - 0048|swansea|carmarthenshire|united kingdom` — added _(2026-05-12)_
- `locations.local institution|cambridge|cambridgeshire|united kingdom` — added _(2026-05-12)_
- `locations.local institution|solna||sweden` — added _(2026-05-12)_
- `locations.local institution|gothenberg||sweden` — added _(2026-05-12)_
- `locations.local institution|madrid||spain` — added _(2026-05-12)_
- `locations.local institution - 0064|l'hospitalet de llobregat||spain` — added _(2026-05-12)_
- `locations.local institution|barcelona||spain` — added _(2026-05-12)_
- `locations.local institution|pamplona|navarre|spain` — added _(2026-05-12)_
- `locations.local institution|saint petersburg||russia` — added _(2026-05-12)_
- `locations.local institution|moscow||russia` — added _(2026-05-12)_
- `locations.local institution|timișoara||romania` — added _(2026-05-12)_
- `locations.local institution|iași||romania` — added _(2026-05-12)_
- `locations.local institution|craiova||romania` — added _(2026-05-12)_
- `locations.local institution|bucharest||romania` — added _(2026-05-12)_
- `locations.local institution|wroclaw||poland` — added _(2026-05-12)_
- `locations.local institution|warsaw||poland` — added _(2026-05-12)_
- `locations.local institution|rybnik||poland` — added _(2026-05-12)_
- `locations.local institution|poznan||poland` — added _(2026-05-12)_
- `locations.local institution|lodz||poland` — added _(2026-05-12)_
- `locations.local institution|gdansk||poland` — added _(2026-05-12)_
- `locations.local institution|lorenskog||norway` — added _(2026-05-12)_
- `locations.local institution|bergen||norway` — added _(2026-05-12)_
- `locations.local institution|tokyo||japan` — added _(2026-05-12)_
- `locations.local institution|kumamoto||japan` — added _(2026-05-12)_
- `locations.local institution|kobe-city, hyogo||japan` — added _(2026-05-12)_
- `locations.local institution|yamagata|yamagata|japan` — added _(2026-05-12)_
- `locations.local institution|tokushima|tokushima|japan` — added _(2026-05-12)_
- `locations.local institution - 0167|hamamatsu|shizuoka|japan` — added _(2026-05-12)_
- `locations.local institution - 0169|suita|osaka|japan` — added _(2026-05-12)_
- `locations.local institution|osaka-sayama-shi|osaka|japan` — added _(2026-05-12)_
- `locations.local institution|kyoto|kyoto|japan` — added _(2026-05-12)_
- `locations.local institution|yokohama|kanagawa|japan` — added _(2026-05-12)_
- `locations.local institution|morioka|iwate|japan` — added _(2026-05-12)_
- `locations.local institution|sapporo|hokkaido|japan` — added _(2026-05-12)_
- `locations.local institution|higashiku|fukuoka|japan` — added _(2026-05-12)_
- `locations.local institution|chiba|chiba|japan` — added _(2026-05-12)_
- `locations.local institution|akita|akita|japan` — added _(2026-05-12)_
- `locations.local institution|terni||italy` — added _(2026-05-12)_
- `locations.local institution|siena||italy` — added _(2026-05-12)_
- `locations.local institution - 0102|rozzano||italy` — added _(2026-05-12)_
- `locations.local institution|roma||italy` — added _(2026-05-12)_
- `locations.local institution|rimini||italy` — added _(2026-05-12)_
- `locations.local institution - 0082|milan||italy` — added _(2026-05-12)_
- `locations.local institution|meldola (fc)||italy` — added _(2026-05-12)_
- `locations.local institution|arezzo||italy` — added _(2026-05-12)_
- `locations.local institution|tel aviv||israel` — added _(2026-05-12)_
- `locations.local institution|ramat gan||israel` — added _(2026-05-12)_
- `locations.local institution - 0148|petah tikva||israel` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT01668784.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT01668784*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*