---
title: Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
nct_id: NCT03937219
overall_status: ACTIVE_NOT_RECRUITING
phase: PHASE3
sponsor: Exelixis
study_type: INTERVENTIONAL
primary_condition: Renal Cell Carcinoma
countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Mexico, Netherlands, New Zealand, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT03937219.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT03937219"
ct_last_update_post_date: 2025-09-10
last_seen_at: "2026-05-12T06:30:32.484Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

**Official Title:** A Randomized, Double-Blind, Controlled Phase 3 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab Versus Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma of Intermediate or Poor Risk

**NCT ID:** [NCT03937219](https://clinicaltrials.gov/study/NCT03937219)

## Key Facts

- **Status:** ACTIVE_NOT_RECRUITING
- **Phase:** PHASE3
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 855
- **Lead Sponsor:** Exelixis
- **Conditions:** Renal Cell Carcinoma
- **Start Date:** 2019-06-25
- **Completion Date:** 2027-01-31
- **CT.gov Last Update:** 2025-09-10

## Brief Summary

This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio at approximately 180 sites.

## Detailed Description

This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. The primary objective of this study is to evaluate the effect of cabozantinib in combination with nivolumab and ipilimumab ("triplet") on the duration of progression-free survival (PFS) versus nivolumab and ipilimumab. A secondary objective is to evaluate the effect of triplet combination on the duration of overall survival (OS).

## Eligibility

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

```
Inclusion Criteria:

* Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
* Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.
* Measurable disease per RECIST 1.1 as determined by the Investigator. Measurable disease must be outside the radiation field if radiation therapy was previously administered.
* Karnofsky Performance Status (KPS) ≥ 70%.
* Adequate organ and marrow function.

Exclusion Criteria:

* Prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents.
* Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and stable for at least 4 weeks prior to randomization.
* Concomitant anticoagulation with oral anticoagulants or platelet inhibitors.
* Administration of a live, attenuated vaccine within 30 days prior to randomization.
* Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesions invading major pulmonary blood vessels.
* Other clinically significant disorders such as:

  * Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomization.
  * Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization.
  * Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active myobacterial infection.
  * Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to randomization.
* Major surgery (eg, nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major or minor surgery before randomization.
* Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
```

## Arms

- **Experimental Arm** (EXPERIMENTAL) — Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
- **Control Arm** (ACTIVE_COMPARATOR) — Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab

## Interventions

- **Cabozantinib** (DRUG) — Specified dose on specified days.
- **Nivolumab** (BIOLOGICAL) — Specified dose on specified days.
- **Ipilimumab** (BIOLOGICAL) — Specified dose on specified days.
- **Cabozantinib-matched placebo** (DRUG) — Specified dose on specified days.

## Primary Outcomes

- **Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC)** _(time frame: Up to 32 months)_ — Duration of PFS was defined as the time from randomization to the earlier of either the date of radiographic progression per BIRC or the date of death due to any cause. PFS (months) = (earliest date of progression, death, censoring - date of randomization + 1)/30.4375. PFS was determined as per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1.

## Secondary Outcomes

- **Duration of Overall Survival (OS)** _(time frame: Up to 58 months)_

## Locations (159)

- Exelixis Clinical Site #116, La Jolla, California, United States
- Exelixis Clinical Site #166, Orange, California, United States
- Exelixis Clinical Site #29, Boca Raton, Florida, United States
- Exelixis Clinical Site #44, Miami, Florida, United States
- Exelixis Clinical Site #3, Atlanta, Georgia, United States
- Exelixis Clinical Site #95, Chicago, Illinois, United States
- Exelixis Clinical Site #69, Scarborough, Maine, United States
- Exelixis Clinical Site #58A, Baltimore, Maryland, United States
- Exelixis Clinical Site #7B, Boston, Massachusetts, United States
- Exelixis Clinical Site #7A, Boston, Massachusetts, United States
- Exelixis Clinical Site #7C, Boston, Massachusetts, United States
- Exelixis Clinical Site #6, Burlington, Massachusetts, United States
- Exelixis Clinical Site #15, Detroit, Michigan, United States
- Exelixis Clinical Site #24, Kansas City, Missouri, United States
- Exelixis Clinical Site #4, St Louis, Missouri, United States
- Exelixis Clinical Site #2, Omaha, Nebraska, United States
- Exelixis Clinical Site #159, New York, New York, United States
- Exelixis Clinical Site #8, New York, New York, United States
- Exelixis Clinical Site #19, Syracuse, New York, United States
- Exelixis Clinical Site #101, Charlotte, North Carolina, United States
- Exelixis Clinical Site #107, Portland, Oregon, United States
- Exelixis Clinical Site #12, Pittsburgh, Pennsylvania, United States
- Exelixis Clinical Site #102, Charleston, South Carolina, United States
- Exelixis Clinical Site #5, Myrtle Beach, South Carolina, United States
- Exelixis Clinical Site #10, Nashville, Tennessee, United States
- Exelixis Clinical Site #38, Nashville, Tennessee, United States
- Exelixis Clinical Site #64, Fairfax, Virginia, United States
- Exelixis Clinical Site #57, Seattle, Washington, United States
- Exelixis Clinical Site #1, Spokane, Washington, United States
- Exelixis Clinical Site #13, Madison, Wisconsin, United States
- Exelixis Clinical Site #153, Pilar, Buenos Aires, Argentina
- Exelixis Clinical Site #109, Rosario, Santa Fe Province, Argentina
- Exelixis Clinical Site #73, San Miguel de Tucumán, Tucumán Province, Argentina
- Exelixis Clinical Site #54, Buenos Aires, Argentina
- Exelixis Clinical Site #63, CABA, Argentina
- Exelixis Clinical Site #110, Ciudad Autonoma de Buenos Aire, Argentina
- Exelixis Clinical Site #120, Córdoba, Argentina
- Exelixis Clinical Site #32, Albury, New South Wales, Australia
- Exelixis Clinical Site #35, Kogarah, New South Wales, Australia
- Exelixis Clinical Site #27, North Ryde, New South Wales, Australia
- Exelixis Clinical Site #33, Sydney, New South Wales, Australia
- Exelixis Clinical Site #17, South Brisbane, Queensland, Australia
- Exelixis Clinical Site #14, Woolloongabba, Queensland, Australia
- Exelixis Clinical Site #18, Adelaide, South Australia, Australia
- Exelixis Clinical Site #11, North Adelaide, South Australia, Australia
- Exelixis Clinical Site #9, Ballarat, Victoria, Australia
- Exelixis Clinical Site #23, Box Hill, Victoria, Australia
- Exelixis Clinical Site #26, Subiaco, Western Australia, Australia
- Exelixis Clinical Site #98, Wiener Neustadt, Lower Austria, Austria
- Exelixis Clinical Site #76, Linz, Upper Austria, Austria
- Exelixis Clinical Site #75, Salzburg, Austria
- Exelixis Clinical Site #126, Vienna, Austria
- Exelixis Clinical Site #112, Brussels, Belgium
- Exelixis Clinical Site #146, Hasselt, Belgium
- Exelixis Clinical Site #154, Belo Horizonte, Minas Gerais, Brazil
- Exelixis Clinical Site #155, Curitiba, Paraná, Brazil
- Exelixis Clinical Site #158, Porto Alegre, Rio Grande do Sul, Brazil
- Exelixis Clinical Site #140, Porto Alegre, Rio Grande do Sul, Brazil
- Exelixis Clinical Site #163, Porto Alegre, Rio Grande do Sul, Brazil
- Exelixis Clinical Site #168, Barretos, São Paulo, Brazil
- Exelixis Clinical Site #162, São José do Rio Preto, São Paulo, Brazil
- Exelixis Clinical Site #119, São Paulo, Brazil
- Exelixis Clinical Site #141, São Paulo, Brazil
- Exelixis Clinical Site #22, Calgary, Alberta, Canada
- Exelixis Clinical Site #105, Winnipeg, Manitoba, Canada
- Exelixis Clinical Site #46, Ottawa, Ontario, Canada
- Exelixis Clinical Site #25, Toronto, Ontario, Canada
- Exelixis Clinical Site #113, Montreal, Quebec, Canada
- Exelixis Clinical Site #85, Temuco, Región de La Araucanía (IX), Chile
- Exelixis Clinical Site #91, Santiago, Chile
- Exelixis Clinical Site #100, Santiago, Chile
- Exelixis Clinical Site #89, Králová, Czechia
- Exelixis Clinical Site #114, Prague, Czechia
- Exelixis Clinical Site #118, Prague, Czechia
- Exelixis Clinical Site #50, Helsinki, Finland
- Exelixis Clinical Site #56, Tampere, Finland
- Exelixis Clinical Site #52, Turku, Finland
- Exelixis Clinical Site #86, Bordeaux, France
- Exelixis Clinical Site #71, Le Mans, France
- Exelixis Clinical Site #78, Lyon, France
- Exelixis Clinical Site #80, Montpellier, France
- Exelixis Clinical Site #66, Nice, France
- Exelixis Clinical Site #150, Paris, France
- Exelixis Clinical Site #65, Reims, France
- Exelixis Clinical Site #125, Rennes, France
- Exelixis Clinical Site #128, Strasbourg, France
- Exelixis Clinical Site #90, Strasbourg, France
- Exelixis Clinical Site #42, Toulouse, France
- Exelixis Clinical Site #67, Vandœuvre-lès-Nancy, France
- Exelixis Clinical Site #37, Villejuif, France
- Exelixis Clinical Site #127, Heidelberg, Baden-Wurttemberg, Germany
- Exelixis Clinical Site #115, Tübingen, Baden-Wurttemberg, Germany
- Exelixis Clinical Site #117, Frankfurt am Main, Hesse, Germany
- Exelixis Clinical Site #139, Münster, North Rhine-Westphalia, Germany
- Exelixis Clinical Site #171, Münster, North Rhine-Westphalia, Germany
- Exelixis Clinical Site #164, Mainz, Rhineland-Palatinate, Germany
- Exelixis Clinical Site #137, Jena, Thuringia, Germany
- Exelixis Clinical Site #124, Dresden, Germany
- Exelixis Clinical Site #28, Hong Kong, Hong Kong
- Exelixis Clinical Site #136, Shatin, Hong Kong
- Exelixis Clinical Site #111, Tuenmen, Hong Kong
- Exelixis Clinical Site #39, Budapest, Hungary
- Exelixis Clinical Site #51, Pécs, Hungary
- Exelixis Clinical Site #88, Beersheba, Israel
- Exelixis Clinical Site #81, Haifa, Israel
- Exelixis Clinical Site #84, Jerusalem, Israel
- Exelixis Clinical Site #121, Kfar Saba, Israel
- Exelixis Clinical Site #97, Petah Tikva, Israel
- Exelixis Clincal Site #129, Ramat Gan, Israel
- Exelixis Clinical Site #41, Meldola, Forli - Cesena, Italy
- Exelixis Clinical Site #70, Faenza, Ravenna, Italy
- Exelixis Clinical Site #47, Arezzo, Italy
- Exelixis Clinical Site #60, Modena, Italy
- Exelixis Clinical Site #61, Padova, Italy
- Exelixis Clinical Site #59, Pavia, Italy
- Exelixis Clinical Site #104, Perugia, Italy
- Exelixis Clinical Site #68, Terni, Italy
- Exelixis Clinical Site #123, Aguascalientes, Aguascalientes, Mexico
- Exelixis Clinical Site #167, León, Guanajuato, Mexico
- Exelixis Clinical Site #169, Zapopan, Jalisco, Mexico
- Exelixis Clinical Site #134, Monterrey, Nuevo León, Mexico
- Exelixis Clinical Site #132, Oaxaca City, Oaxaca, Mexico
- Exelixis Clinical Site #160, Mexico City, Mexico
- Exelixis Clinical Site #131, Querétaro, Mexico
- Exelixis Clinical Site #161, Querétaro, Mexico
- Exelixis Clinical Site #144, Amsterdam, Netherlands
- Exelixis Clinical Site #149, Rotterdam, Netherlands
- Exelixis Clinical Site #122, Hamilton, Waikato Region, New Zealand
- Exelixis Clinical Site #148, Newtown, Wellington Region, New Zealand
- Exelixis Clinical Site #31, Biała Podlaska, Poland
- Exelixis Clinical Site #62, Bydgoszcz, Poland
- Exelixis Clinical Site #135, Gdansk, Poland
- Exelixis Clinical Site #99, Otwock, Poland
- Exelixis Clinical Site #83, Poznan, Poland
- Exelixis Clinical Site #77, Singapore, Singapore
- Exelixis Clinical Site #40, Singapore, Singapore
- Exelixis Clinical Site #147, Seongnam-si, Gyeonggi-do, South Korea
- Exelixis Clinical Site #143, Seoul, South Korea
- Exelixis Clinical Site #151, Seoul, South Korea
- Exelixis Clinical Site #152, Seoul, South Korea
- Exelixis Clinical Site #53, Santiago de Compostela, Coruña, Spain
- Exelixis Clinical Site #45, Pamplona, Navarre, Spain
- Exelixis Clinical Site #43, Barcelona, Spain
- Exelixis Clinical Site #36, Barcelona, Spain
- Exelixis Clinical Site #49, Córdoba, Spain
- Exelixis Clinical Site #34, Madrid, Spain
- Exelixis Clinical Site #94, Madrid, Spain
- Exelixis Clinical Site #20, Madrid, Spain
- Exelixis Clinical Site #55, Madrid, Spain
- Exelixis Clinical Site #96, Oviedo, Spain
- Exelixis Clinical Site #74, Valencia, Spain
- Exelixis Clinical Site #142, Taichung, Taiwan
- Exelixis Clinical Site #138, Taipei, Taiwan
- Exelixis Clinical Site #173, Taoyuan, Taiwan
- Exelixis Clinical Site #72, Cambridge, United Kingdom
- Exelixis Clinical Site #93, Glasgow, United Kingdom
- Exelixis Clinical Site #30, London, United Kingdom
- Exelixis Clinical Site #172, London, United Kingdom
- Exelixis Clinical Site #92, Manchester, United Kingdom

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `locations.exelixis clinical site #3|atlanta|georgia|united states` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.exelixis clinical site #116|la jolla|california|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #166|orange|california|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #29|boca raton|florida|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #44|miami|florida|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #95|chicago|illinois|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #69|scarborough|maine|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #58a|baltimore|maryland|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #7b|boston|massachusetts|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #7a|boston|massachusetts|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #7c|boston|massachusetts|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #6|burlington|massachusetts|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #15|detroit|michigan|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #24|kansas city|missouri|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #4|st louis|missouri|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #2|omaha|nebraska|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #159|new york|new york|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #8|new york|new york|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #19|syracuse|new york|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #101|charlotte|north carolina|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #107|portland|oregon|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #12|pittsburgh|pennsylvania|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #102|charleston|south carolina|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #5|myrtle beach|south carolina|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #10|nashville|tennessee|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #38|nashville|tennessee|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #64|fairfax|virginia|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #57|seattle|washington|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #1|spokane|washington|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #13|madison|wisconsin|united states` — added _(2026-05-12)_
- `locations.exelixis clinical site #153|pilar|buenos aires|argentina` — added _(2026-05-12)_
- `locations.exelixis clinical site #109|rosario|santa fe province|argentina` — added _(2026-05-12)_
- `locations.exelixis clinical site #73|san miguel de tucumán|tucumán province|argentina` — added _(2026-05-12)_
- `locations.exelixis clinical site #54|buenos aires||argentina` — added _(2026-05-12)_
- `locations.exelixis clinical site #63|caba||argentina` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT03937219.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT03937219*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*