Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)

August 22, 2025 updated by: Exelixis

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

855

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1125ABD
        • Exelixis Clinical Site #54
      • CABA, Argentina, C1120AAT
        • Exelixis Clinical Site #63
      • Ciudad Autonoma de Buenos Aire, Argentina, C1426ANZ
        • Exelixis Clinical Site #110
      • Córdoba, Argentina, X5004
        • Exelixis Clinical Site #120
    • Buenos Aires
      • Pilar, Buenos Aires, Argentina, B1629ODT
        • Exelixis Clinical Site #153
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, S2000KZE
        • Exelixis Clinical Site #109
    • Tucumán Province
      • San Miguel de Tucumán, Tucumán Province, Argentina, T4000
        • Exelixis Clinical Site #73
  • Australia
    • New South Wales
      • Albury, New South Wales, Australia, 2640
        • Exelixis Clinical Site #32
      • Kogarah, New South Wales, Australia, 2217
        • Exelixis Clinical Site #35
      • North Ryde, New South Wales, Australia, 2109
        • Exelixis Clinical Site #27
      • Sydney, New South Wales, Australia, 2065
        • Exelixis Clinical Site #33
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Exelixis Clinical Site #17
      • Woolloongabba, Queensland, Australia, 4102
        • Exelixis Clinical Site #14
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Exelixis Clinical Site #18
      • North Adelaide, South Australia, Australia, 5006
        • Exelixis Clinical Site #11
    • Victoria
      • Ballarat, Victoria, Australia, 3350
        • Exelixis Clinical Site #9
      • Box Hill, Victoria, Australia, 3128
        • Exelixis Clinical Site #23
    • Western Australia
      • Subiaco, Western Australia, Australia, 6008
        • Exelixis Clinical Site #26
  • Austria
      • Salzburg, Austria, 5020
        • Exelixis Clinical Site #75
      • Vienna, Austria, 1090
        • Exelixis Clinical Site #126
    • Lower Austria
      • Wiener Neustadt, Lower Austria, Austria, 2700
        • Exelixis Clinical Site #98
    • Upper Austria
      • Linz, Upper Austria, Austria, 4020
        • Exelixis Clinical Site #76
  • Belgium
      • Brussels, Belgium, 1000
        • Exelixis Clinical Site #112
      • Hasselt, Belgium, 3500
        • Exelixis Clinical Site #146
  • Brazil
      • São Paulo, Brazil, 01323-001
        • Exelixis Clinical Site #119
      • São Paulo, Brazil, 01327-001
        • Exelixis Clinical Site #141
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30130-090
        • Exelixis Clinical Site #154
    • Paraná
      • Curitiba, Paraná, Brazil, 80530-010
        • Exelixis Clinical Site #155
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
        • Exelixis Clinical Site #158
      • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
        • Exelixis Clinical Site #140
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Exelixis Clinical Site #163
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Exelixis Clinical Site #168
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Exelixis Clinical Site #162
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Exelixis Clinical Site #22
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • Exelixis Clinical Site #105
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Exelixis Clinical Site #46
      • Toronto, Ontario, Canada, M4N 3M5
        • Exelixis Clinical Site #25
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Exelixis Clinical Site #113
  • Chile
      • Santiago, Chile, 7500921
        • Exelixis Clinical Site #91
      • Santiago, Chile, 8420383
        • Exelixis Clinical Site #100
    • Región de La Araucanía (IX)
      • Temuco, Región de La Araucanía (IX), Chile, 4810561
        • Exelixis Clinical Site #85
  • Czechia
      • Králová, Czechia, 50005
        • Exelixis Clinical Site #89
      • Prague, Czechia, 140 59
        • Exelixis Clinical Site #114
      • Prague, Czechia, 150 06
        • Exelixis Clinical Site #118
  • Finland
      • Helsinki, Finland, 00029
        • Exelixis Clinical Site #50
      • Tampere, Finland, 33520
        • Exelixis Clinical Site #56
      • Turku, Finland, 20520
        • Exelixis Clinical Site #52
  • France
      • Bordeaux, France, 33075
        • Exelixis Clinical Site #86
      • Le Mans, France, 72000
        • Exelixis Clinical Site #71
      • Lyon, France, 69373
        • Exelixis Clinical Site #78
      • Montpellier, France, 34295
        • Exelixis Clinical Site #80
      • Nice, France, 06189
        • Exelixis Clinical Site #66
      • Paris, France, 75015
        • Exelixis Clinical Site #150
      • Reims, France, 51726
        • Exelixis Clinical Site #65
      • Rennes, France, 35042
        • Exelixis Clinical Site #125
      • Strasbourg, France, 67000
        • Exelixis Clinical Site #128
      • Strasbourg, France, 67200
        • Exelixis Clinical Site #90
      • Toulouse, France, 31059
        • Exelixis Clinical Site #42
      • Vandœuvre-lès-Nancy, France, 54519
        • Exelixis Clinical Site #67
      • Villejuif, France, 94800
        • Exelixis Clinical Site #37
  • Germany
      • Dresden, Germany, 01307
        • Exelixis Clinical Site #124
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
        • Exelixis Clinical Site #127
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Exelixis Clinical Site #115
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 60596
        • Exelixis Clinical Site #117
    • North Rhine-Westphalia
      • Münster, North Rhine-Westphalia, Germany, 48149
        • Exelixis Clinical Site #139
      • Münster, North Rhine-Westphalia, Germany, 90419
        • Exelixis Clinical Site #171
    • Rhineland-Palatinate
      • Mainz, Rhineland-Palatinate, Germany, 55131
        • Exelixis Clinical Site #164
    • Thuringia
      • Jena, Thuringia, Germany, 077477
        • Exelixis Clinical Site #137
  • Hong Kong
      • Hong Kong, Hong Kong
        • Exelixis Clinical Site #28
      • Shatin, Hong Kong
        • Exelixis Clinical Site #136
      • Tuenmen, Hong Kong
        • Exelixis Clinical Site #111
  • Hungary
      • Budapest, Hungary, 1122
        • Exelixis Clinical Site #39
      • Pécs, Hungary, 7624
        • Exelixis Clinical Site #51
  • Israel
      • Beersheba, Israel, 84101
        • Exelixis Clinical Site #88
      • Haifa, Israel, 3109601
        • Exelixis Clinical Site #81
      • Jerusalem, Israel, 9112001
        • Exelixis Clinical Site #84
      • Kfar Saba, Israel, 4428164
        • Exelixis Clinical Site #121
      • Petah Tikva, Israel, 49100
        • Exelixis Clinical Site #97
      • Ramat Gan, Israel, 5265601
        • Exelixis Clincal Site #129
  • Italy
      • Arezzo, Italy, 52100
        • Exelixis Clinical Site #47
      • Modena, Italy, 41124
        • Exelixis Clinical Site #60
      • Padua, Italy, 35128
        • Exelixis Clinical Site #61
      • Pavia, Italy, 27100
        • Exelixis Clinical Site #59
      • Perugia, Italy, 06132
        • Exelixis Clinical Site #104
      • Terni, Italy, 05100
        • Exelixis Clinical Site #68
    • Forli - Cesena
      • Meldola, Forli - Cesena, Italy, 47014
        • Exelixis Clinical Site #41
    • Ravenna
      • Faenza, Ravenna, Italy, 48018
        • Exelixis Clinical Site #70
  • Mexico
      • Mexico City, Mexico, 03100
        • Exelixis Clinical Site #160
      • Querétaro, Mexico, 76000
        • Exelixis Clinical Site #131
      • Querétaro, Mexico, 76090
        • Exelixis Clinical Site #161
    • Aguascalientes
      • Aguascalientes, Aguascalientes, Mexico, 20116
        • Exelixis Clinical Site #123
    • Guanajuato
      • León, Guanajuato, Mexico, 37000
        • Exelixis Clinical Site #167
    • Jalisco
      • Zapopan, Jalisco, Mexico, 45070
        • Exelixis Clinical Site #169
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64710
        • Exelixis Clinical Site #134
    • Oaxaca
      • Oaxaca City, Oaxaca, Mexico, 68000
        • Exelixis Clinical Site #132
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Exelixis Clinical Site #144
      • Rotterdam, Netherlands, 3015 GD
        • Exelixis Clinical Site #149
  • New Zealand
    • Waikato Region
      • Hamilton, Waikato Region, New Zealand, 3204
        • Exelixis Clinical Site #122
    • Wellington Region
      • Newtown, Wellington Region, New Zealand, 6021
        • Exelixis Clinical Site #148
  • Poland
      • Biała Podlaska, Poland, 21-500
        • Exelixis Clinical Site #31
      • Bydgoszcz, Poland, 85-796
        • Exelixis Clinical Site #62
      • Gdansk, Poland, 80-219
        • Exelixis Clinical Site #135
      • Otwock, Poland, 05-400
        • Exelixis Clinical Site #99
      • Poznan, Poland, 60-693
        • Exelixis Clinical Site #83
  • Singapore
      • Singapore, Singapore, 119074
        • Exelixis Clinical Site #77
      • Singapore, Singapore, 169610
        • Exelixis Clinical Site #40
  • South Korea
      • Seoul, South Korea, 03722
        • Exelixis Clinical Site #143
      • Seoul, South Korea, 05505
        • Exelixis Clinical Site #151
      • Seoul, South Korea, 06351
        • Exelixis Clinical Site #152
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, South Korea, 13620
        • Exelixis Clinical Site #147
  • Spain
      • Barcelona, Spain, 08035
        • Exelixis Clinical Site #43
      • Barcelona, Spain, 08036
        • Exelixis Clinical Site #36
      • Córdoba, Spain, 14004
        • Exelixis Clinical Site #49
      • Madrid, Spain, 28009
        • Exelixis Clinical Site #34
      • Madrid, Spain, 28040
        • Exelixis Clinical Site #94
      • Madrid, Spain, 28041
        • Exelixis Clinical Site #20
      • Madrid, Spain, 28050
        • Exelixis Clinical Site #55
      • Oviedo, Spain, 33011
        • Exelixis Clinical Site #96
      • Valencia, Spain, 46009
        • Exelixis Clinical Site #74
    • Coruña
      • Santiago de Compostela, Coruña, Spain, 15706
        • Exelixis Clinical Site #53
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Exelixis Clinical Site #45
  • Taiwan
      • Taichung, Taiwan, 404
        • Exelixis Clinical Site #142
      • Taipei, Taiwan, 10002
        • Exelixis Clinical Site #138
      • Taoyuan District, Taiwan, 333
        • Exelixis Clinical Site #173
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Exelixis Clinical Site #72
      • Glasgow, United Kingdom, G12 0YN
        • Exelixis Clinical Site #93
      • London, United Kingdom, EC1A 7BE
        • Exelixis Clinical Site #30
      • London, United Kingdom, W6 8RF
        • Exelixis Clinical Site #172
      • Manchester, United Kingdom, M20 4BX
        • Exelixis Clinical Site #92
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Exelixis Clinical Site #116
      • Orange, California, United States, 92868-3201
        • Exelixis Clinical Site #166
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Exelixis Clinical Site #29
      • Miami, Florida, United States, 33176
        • Exelixis Clinical Site #44
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Exelixis Clinical Site #3
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Exelixis Clinical Site #95
    • Maine
      • Scarborough, Maine, United States, 04074
        • Exelixis Clinical Site #69
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Exelixis Clinical Site #58A
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Exelixis Clinical Site #7B
      • Boston, Massachusetts, United States, 02215
        • Exelixis Clinical Site #7A
      • Boston, Massachusetts, United States, 02215
        • Exelixis Clinical Site #7C
      • Burlington, Massachusetts, United States, 01805
        • Exelixis Clinical Site #6
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Exelixis Clinical Site #15
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Exelixis Clinical Site #24
      • St Louis, Missouri, United States, 63110
        • Exelixis Clinical Site #4
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Exelixis Clinical Site #2
    • New York
      • New York, New York, United States, 10032
        • Exelixis Clinical Site #159
      • New York, New York, United States, 10065
        • Exelixis Clinical Site #8
      • Syracuse, New York, United States, 13210
        • Exelixis Clinical Site #19
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Exelixis Clinical Site #101
    • Oregon
      • Portland, Oregon, United States, 97239
        • Exelixis Clinical Site #107
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Exelixis Clinical Site #12
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Exelixis Clinical Site #102
      • Myrtle Beach, South Carolina, United States, 29572
        • Exelixis Clinical Site #5
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Exelixis Clinical Site #10
      • Nashville, Tennessee, United States, 37232
        • Exelixis Clinical Site #38
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Exelixis Clinical Site #64
    • Washington
      • Seattle, Washington, United States, 98109
        • Exelixis Clinical Site #57
      • Spokane, Washington, United States, 99208
        • Exelixis Clinical Site #1
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Exelixis Clinical Site #13

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Arm
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
Drug: Cabozantinib
Specified dose on specified days.
Other Names:
  • Cabometyx
  • XL184
Biological: Nivolumab
Specified dose on specified days.
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Specified dose on specified days.
Other Names:
  • BMS-734016
  • Yervoy
Active Comparator: Control Arm
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
Biological: Nivolumab
Specified dose on specified days.
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Specified dose on specified days.
Other Names:
  • BMS-734016
  • Yervoy
Drug: Cabozantinib-matched placebo
Specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 32 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Overall Survival (OS)
Time Frame: Up to 58 months
Duration of OS (months) = (earliest date of death or censoring - date of randomization + 1)/30.4375.
Up to 58 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exelixis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 25, 2019

Primary Completion (Actual)

January 31, 2022

Study Completion (Estimated)

January 31, 2027

Study Registration Dates

First Submitted

May 2, 2019

First Submitted That Met QC Criteria

May 2, 2019

First Posted (Actual)

May 3, 2019

Study Record Updates

Last Update Posted (Estimated)

September 10, 2025

Last Update Submitted That Met QC Criteria

August 22, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XL184-313
  • 2024-515616-47-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Renal Cell Carcinoma

Clinical Trials on Cabozantinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo, DR of

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe