Renal Cell CarcinomaPhase 3COSMIC-313NCT03937219
Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
A Phase 3 study testing Cabozantinib, Nivolumab and Ipilimumab in people with Renal Cell Carcinoma, run by Exelixis at 159 sites in 25 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Cabozantinib, Nivolumab and Ipilimumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 855 participants
- Where
- 159 sitesin 25 countries
- Study dates
- 25 Jun 2019to 31 Jan 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
159 sites in 25 countries.
159 sites in 25 countries
United States30 sites
Exelixis Clinical Site #3
Atlanta, Georgia, 30318
Exelixis Clinical Site #58A
Baltimore, Maryland, 21287
Exelixis Clinical Site #29
Boca Raton, Florida, 33486
Exelixis Clinical Site #7B
Boston, Massachusetts, 02114
Exelixis Clinical Site #7A
Boston, Massachusetts, 02215
Exelixis Clinical Site #7C
Boston, Massachusetts, 02215
Exelixis Clinical Site #6
Burlington, Massachusetts, 01805
Exelixis Clinical Site #102
Charleston, South Carolina, 29425
Exelixis Clinical Site #101
Charlotte, North Carolina, 28204
Exelixis Clinical Site #95
Chicago, Illinois, 60612
Exelixis Clinical Site #15
Detroit, Michigan, 48201
Exelixis Clinical Site #64
Fairfax, Virginia, 22031
Exelixis Clinical Site #24
Kansas City, Missouri, 64132
Exelixis Clinical Site #116
La Jolla, California, 92093
Exelixis Clinical Site #13
Madison, Wisconsin, 53792
Exelixis Clinical Site #44
Miami, Florida, 33176
Exelixis Clinical Site #5
Myrtle Beach, South Carolina, 29572
Exelixis Clinical Site #10
Nashville, Tennessee, 37203
Exelixis Clinical Site #38
Nashville, Tennessee, 37232
Exelixis Clinical Site #159
New York, New York, 10032
Exelixis Clinical Site #8
New York, New York, 10065
Exelixis Clinical Site #2
Omaha, Nebraska, 68130
Exelixis Clinical Site #166
Orange, California, 92868-3201
Exelixis Clinical Site #12
Pittsburgh, Pennsylvania, 15232
Exelixis Clinical Site #107
Portland, Oregon, 97239
Exelixis Clinical Site #69
Scarborough, Maine, 04074
Exelixis Clinical Site #57
Seattle, Washington, 98109
Exelixis Clinical Site #1
Spokane, Washington, 99208
Exelixis Clinical Site #4
St Louis, Missouri, 63110
Exelixis Clinical Site #19
Syracuse, New York, 13210
France13 sites
Exelixis Clinical Site #86
Bordeaux, 33075
Exelixis Clinical Site #71
Le Mans, 72000
Exelixis Clinical Site #78
Lyon, 69373
Exelixis Clinical Site #80
Montpellier, 34295
Exelixis Clinical Site #66
Nice, 06189
Exelixis Clinical Site #150
Paris, 75015
Exelixis Clinical Site #65
Reims, 51726
Exelixis Clinical Site #125
Rennes, 35042
Exelixis Clinical Site #128
Strasbourg, 67000
Exelixis Clinical Site #90
Strasbourg, 67200
Exelixis Clinical Site #42
Toulouse, 31059
Exelixis Clinical Site #67
Vandœuvre-lès-Nancy, 54519
Exelixis Clinical Site #37
Villejuif, 94800
Australia11 sites
Exelixis Clinical Site #18
Adelaide, South Australia, 5000
Exelixis Clinical Site #32
Albury, New South Wales, 2640
Exelixis Clinical Site #9
Ballarat, Victoria, 3350
Exelixis Clinical Site #23
Box Hill, Victoria, 3128
Exelixis Clinical Site #35
Kogarah, New South Wales, 2217
Exelixis Clinical Site #11
North Adelaide, South Australia, 5006
Exelixis Clinical Site #27
North Ryde, New South Wales, 2109
Exelixis Clinical Site #17
South Brisbane, Queensland, 4101
Exelixis Clinical Site #26
Subiaco, Western Australia, 6008
Exelixis Clinical Site #33
Sydney, New South Wales, 2065
Exelixis Clinical Site #14
Woolloongabba, Queensland, 4102
Spain11 sites
Exelixis Clinical Site #43
Barcelona, 08035
Exelixis Clinical Site #36
Barcelona, 08036
Exelixis Clinical Site #49
Córdoba, 14004
Exelixis Clinical Site #34
Madrid, 28009
Exelixis Clinical Site #94
Madrid, 28040
Exelixis Clinical Site #20
Madrid, 28041
Exelixis Clinical Site #55
Madrid, 28050
Exelixis Clinical Site #96
Oviedo, 33011
Exelixis Clinical Site #45
Pamplona, Navarre, 31008
Exelixis Clinical Site #53
Santiago de Compostela, Coruña, 15706
Exelixis Clinical Site #74
Valencia, 46009
Brazil9 sites
Exelixis Clinical Site #168
Barretos, São Paulo, 14784-400
Exelixis Clinical Site #154
Belo Horizonte, Minas Gerais, 30130-090
Exelixis Clinical Site #155
Curitiba, Paraná, 80530-010
Exelixis Clinical Site #158
Porto Alegre, Rio Grande do Sul, 90050-170
Exelixis Clinical Site #140
Porto Alegre, Rio Grande do Sul, 90110-270
Exelixis Clinical Site #163
Porto Alegre, Rio Grande do Sul, 90610-000
Exelixis Clinical Site #162
São José do Rio Preto, São Paulo, 15090-000
Exelixis Clinical Site #119
São Paulo, 01323-001
Exelixis Clinical Site #141
São Paulo, 01327-001
Germany8 sites
Exelixis Clinical Site #124
Dresden, 01307
Exelixis Clinical Site #117
Frankfurt am Main, Hesse, 60596
Exelixis Clinical Site #127
Heidelberg, Baden-Wurttemberg, 69120
Exelixis Clinical Site #137
Jena, Thuringia, 077477
Exelixis Clinical Site #164
Mainz, Rhineland-Palatinate, 55131
Exelixis Clinical Site #139
Münster, North Rhine-Westphalia, 48149
Exelixis Clinical Site #171
Münster, North Rhine-Westphalia, 90419
Exelixis Clinical Site #115
Tübingen, Baden-Wurttemberg, 72076
Italy8 sites
Exelixis Clinical Site #47
Arezzo, 52100
Exelixis Clinical Site #70
Faenza, Ravenna, 48018
Exelixis Clinical Site #41
Meldola, Forli - Cesena, 47014
Exelixis Clinical Site #60
Modena, 41124
Exelixis Clinical Site #61
Padova, 35128
Exelixis Clinical Site #59
Pavia, 27100
Exelixis Clinical Site #104
Perugia, 06132
Exelixis Clinical Site #68
Terni, 05100
Mexico8 sites
Exelixis Clinical Site #123
Aguascalientes, Aguascalientes, 20116
Exelixis Clinical Site #167
León, Guanajuato, 37000
Exelixis Clinical Site #160
Mexico City, 03100
Exelixis Clinical Site #134
Monterrey, Nuevo León, 64710
Exelixis Clinical Site #132
Oaxaca City, Oaxaca, 68000
Exelixis Clinical Site #131
Querétaro, 76000
Exelixis Clinical Site #161
Querétaro, 76090
Exelixis Clinical Site #169
Zapopan, Jalisco, 45070
Argentina7 sites
Exelixis Clinical Site #54
Buenos Aires, C1125ABD
Exelixis Clinical Site #63
CABA, C1120AAT
Exelixis Clinical Site #110
Ciudad Autonoma de Buenos Aire, C1426ANZ
Exelixis Clinical Site #120
Córdoba, X5004
Exelixis Clinical Site #153
Pilar, Buenos Aires, B1629ODT
Exelixis Clinical Site #109
Rosario, Santa Fe Province, S2000KZE
Exelixis Clinical Site #73
San Miguel de Tucumán, Tucumán Province, T4000
Israel6 sites
Exelixis Clinical Site #88
Beersheba, 84101
Exelixis Clinical Site #81
Haifa, 3109601
Exelixis Clinical Site #84
Jerusalem, 9112001
Exelixis Clinical Site #121
Kfar Saba, 4428164
Exelixis Clinical Site #97
Petah Tikva, 49100
Exelixis Clincal Site #129
Ramat Gan, 5265601
Canada5 sites
Exelixis Clinical Site #22
Calgary, Alberta, T2N 4N2
Exelixis Clinical Site #113
Montreal, Quebec, H3T 1E2
Exelixis Clinical Site #46
Ottawa, Ontario, K1H 8L6
Exelixis Clinical Site #25
Toronto, Ontario, M4N 3M5
Exelixis Clinical Site #105
Winnipeg, Manitoba, R3E 0V9
Poland5 sites
Exelixis Clinical Site #31
Biała Podlaska, 21-500
Exelixis Clinical Site #62
Bydgoszcz, 85-796
Exelixis Clinical Site #135
Gdansk, 80-219
Exelixis Clinical Site #99
Otwock, 05-400
Exelixis Clinical Site #83
Poznan, 60-693
United Kingdom5 sites
Exelixis Clinical Site #72
Cambridge, CB2 0QQ
Exelixis Clinical Site #93
Glasgow, G12 0YN
Exelixis Clinical Site #30
London, EC1A 7BE
Exelixis Clinical Site #172
London, W6 8RF
Exelixis Clinical Site #92
Manchester, M20 4BX
Austria4 sites
Exelixis Clinical Site #76
Linz, Upper Austria, 4020
Exelixis Clinical Site #75
Salzburg, 5020
Exelixis Clinical Site #126
Vienna, 1090
Exelixis Clinical Site #98
Wiener Neustadt, Lower Austria, 2700
South Korea4 sites
Exelixis Clinical Site #147
Seongnam-si, Gyeonggi-do, 13620
Exelixis Clinical Site #143
Seoul, 03722
Exelixis Clinical Site #151
Seoul, 05505
Exelixis Clinical Site #152
Seoul, 06351
Chile3 sites
Exelixis Clinical Site #91
Santiago, 7500921
Exelixis Clinical Site #100
Santiago, 8420383
Exelixis Clinical Site #85
Temuco, Región de La Araucanía (IX), 4810561
Czechia3 sites
Exelixis Clinical Site #89
Králová, 50005
Exelixis Clinical Site #114
Prague, 140 59
Exelixis Clinical Site #118
Prague, 150 06
Finland3 sites
Exelixis Clinical Site #50
Helsinki, 00029
Exelixis Clinical Site #56
Tampere, 33520
Exelixis Clinical Site #52
Turku, 20520
Hong Kong3 sites
Exelixis Clinical Site #28
Hong Kong
Exelixis Clinical Site #136
Shatin
Exelixis Clinical Site #111
Tuenmen
Taiwan3 sites
Exelixis Clinical Site #142
Taichung, 404
Exelixis Clinical Site #138
Taipei, 10002
Exelixis Clinical Site #173
Taoyuan, 333
Belgium2 sites
Exelixis Clinical Site #112
Brussels, 1000
Exelixis Clinical Site #146
Hasselt, 3500
Hungary2 sites
Exelixis Clinical Site #39
Budapest, 1122
Exelixis Clinical Site #51
Pécs, 7624
Netherlands2 sites
Exelixis Clinical Site #144
Amsterdam, 1105 AZ
Exelixis Clinical Site #149
Rotterdam, 3015 GD
New Zealand2 sites
Exelixis Clinical Site #122
Hamilton, Waikato Region, 3204
Exelixis Clinical Site #148
Newtown, Wellington Region, 6021
Singapore2 sites
Exelixis Clinical Site #77
Singapore, 119074
Exelixis Clinical Site #40
Singapore, 169610
About this study
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
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.
Read the 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).
- Conditions
- Renal Cell Carcinoma
- Being tested
- Cabozantinib, Nivolumab, Ipilimumab, Cabozantinib-matched placebo
- Keywords
- renal, cancer, carcinoma
- Medical subject headings
- Carcinoma, Renal Cell, Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called Cabometyx, XL184
Specified dose on specified days.
NivolumabBiological
Also called Opdivo, BMS-936558
Specified dose on specified days.
IpilimumabBiological
Also called Yervoy, BMS-734016
Specified dose on specified days.
Cabozantinib-matched placeboDrug
Specified dose on specified days.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab Receives: Drug: Cabozantinib; Biological: Nivolumab; Biological: Ipilimumab |
| Control Arm | Active comparator | Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab Receives: Biological: Nivolumab; Biological: Ipilimumab; Drug: Cabozantinib-matched placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC)
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.
Measured: Up to 32 months
Secondary outcomes (1)
Duration of Overall Survival (OS)
Duration of OS (months) = (earliest date of death or censoring - date of randomization + 1)/30.4375.
Measured: Up to 58 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2019
- Study start25 Jun 2019
- Primary completion31 Jan 2022
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 855 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937219
- Sponsor's protocol ID
- XL184-313
- Other IDs
- 2024-515616-47-00
- Acronym
- COSMIC-313
- Status last verified
- Sep 2026
- First submitted
- 2 May 2019
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, Yanez Ruiz E, Maruzzo M, Suarez Zaizar A, Fein LE, Schutz FA, Heng DYC, Wang F, Mataveli F, Chang YL, van Kooten Losio M, Suarez C, Motzer RJ; COSMIC-313 Investigators. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med. 2023 May 11;388(19):1767-1778. doi: 10.1056/NEJMoa2212851.
PubMed 37163623Labriola MK, George DJ. Setting a new standard for long-term survival in metastatic kidney cancer. Cancer. 2022 Jun 1;128(11):2058-2060. doi: 10.1002/cncr.34177. Epub 2022 Apr 5. No abstract available.
PubMed 35383907Mar N, Kaakour D, Rezazadeh Kalebasty A. Renal Cell Carcinoma-Lessons in Diversity, Breakthroughs, and Challenges. JCO Oncol Pract. 2022 Mar;18(3):197-199. doi: 10.1200/OP.21.00446. Epub 2021 Sep 22. No abstract available.
PubMed 34550754Hofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.
PubMed 33058158
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03937219
- Acronym / sponsor ID
- COSMIC-313 / XL184-313
- Conditions
- Renal Cell Carcinoma
- Keywords
- renal, cancer, carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 855 participants (actual)
- Lead sponsor
- ExelixisIndustry (pharma, biotech, devices)
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 3 May 2019 (actual)
- Results
- Posted 10 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio.
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Cabozantinib, Biological: Nivolumab, Biological: IpilimumabCabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab |
| Control Arm | Active comparator | Biological: Nivolumab, Biological: Ipilimumab, Drug: Cabozantinib-matched placeboCabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabozantinibAlso: Cabometyx, XL184Specified dose on specified days. | Drug | Experimental Arm |
| NivolumabAlso: Opdivo, BMS-936558Specified dose on specified days. | Biological | Control Arm, Experimental Arm |
| IpilimumabAlso: Yervoy, BMS-734016Specified dose on specified days. | Biological | Control Arm, Experimental Arm |
| Cabozantinib-matched placeboSpecified dose on specified days. | Drug | Control Arm |
Primary outcome
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.
1 secondary outcome
Duration of Overall Survival (OS)
Time frame: Up to 58 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37163623Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, Yanez Ruiz E, Maruzzo M, Suarez Zaizar A, Fein LE, Schutz FA, Heng DYC, Wang F, Mataveli F, Chang YL, van Kooten Losio M, Suarez C, Motzer RJ; COSMIC-313 Investigators. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med. 2023 May 11;388(19):1767-1778. doi: 10.1056/NEJMoa2212851.
- Derived from this study: PubMed 35383907Labriola MK, George DJ. Setting a new standard for long-term survival in metastatic kidney cancer. Cancer. 2022 Jun 1;128(11):2058-2060. doi: 10.1002/cncr.34177. Epub 2022 Apr 5. No abstract available.
- Derived from this study: PubMed 34550754Mar N, Kaakour D, Rezazadeh Kalebasty A. Renal Cell Carcinoma-Lessons in Diversity, Breakthroughs, and Challenges. JCO Oncol Pract. 2022 Mar;18(3):197-199. doi: 10.1200/OP.21.00446. Epub 2021 Sep 22. No abstract available.
- Derived from this study: PubMed 33058158Hofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.
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Solid Tumor, Non-Small Cell Lung Cancer
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A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
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Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
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Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
159 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cabozantinib, Nivolumab and Ipilimumab in people with Renal Cell Carcinoma, run by Exelixis at 159 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 159 sites in United States, France, Australia, Spain, Brazil and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC) (time frame: Up to 32 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03937219, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.