Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

NCT03937219 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: XL184-3132024-515616-47-00
• Study Type: interventional
• Target: 855
• Locations: 24 countries
• Sites: 148

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.

Conditions

Renal Cell Carcinoma

Keywords

renal; cancer; carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 32 months

Secondary Outcomes (1)

• Duration of Overall Survival (OS)

  Up to 58 months

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab

Drug: Cabozantinib; Biological: Nivolumab; Biological: Ipilimumab

Control Arm

ACTIVE COMPARATOR

Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab

Biological: Nivolumab; Biological: Ipilimumab; Drug: Cabozantinib-matched placebo

Interventions

Cabozantinib DRUG

Specified dose on specified days.

Also known as: Cabometyx, XL184

Experimental Arm

Nivolumab BIOLOGICAL

Specified dose on specified days.

Also known as: Opdivo, BMS-936558

Control Arm; Experimental Arm

Ipilimumab BIOLOGICAL

Specified dose on specified days.

Also known as: Yervoy, BMS-734016

Control Arm; Experimental Arm

Cabozantinib-matched placebo DRUG

Specified dose on specified days.

Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (159)

Exelixis Clinical Site #116

La Jolla, California, 92093, United States

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Exelixis Clinical Site #166

Orange, California, 92868-3201, United States

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Exelixis Clinical Site #29

Boca Raton, Florida, 33486, United States

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Exelixis Clinical Site #44

Miami, Florida, 33176, United States

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Exelixis Clinical Site #3

Atlanta, Georgia, 30318, United States

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Exelixis Clinical Site #95

Chicago, Illinois, 60612, United States

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Exelixis Clinical Site #69

Scarborough, Maine, 04074, United States

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Exelixis Clinical Site #58A

Baltimore, Maryland, 21287, United States

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Exelixis Clinical Site #7B

Boston, Massachusetts, 02114, United States

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Exelixis Clinical Site #7A

Boston, Massachusetts, 02215, United States

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Exelixis Clinical Site #7C

Boston, Massachusetts, 02215, United States

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Exelixis Clinical Site #6

Burlington, Massachusetts, 01805, United States

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Exelixis Clinical Site #15

Detroit, Michigan, 48201, United States

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Exelixis Clinical Site #24

Kansas City, Missouri, 64132, United States

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Exelixis Clinical Site #4

St Louis, Missouri, 63110, United States

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Exelixis Clinical Site #2

Omaha, Nebraska, 68130, United States

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Exelixis Clinical Site #159

New York, New York, 10032, United States

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Exelixis Clinical Site #8

New York, New York, 10065, United States

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Exelixis Clinical Site #19

Syracuse, New York, 13210, United States

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Exelixis Clinical Site #101

Charlotte, North Carolina, 28204, United States

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Exelixis Clinical Site #107

Portland, Oregon, 97239, United States

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Exelixis Clinical Site #12

Pittsburgh, Pennsylvania, 15232, United States

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Exelixis Clinical Site #102

Charleston, South Carolina, 29425, United States

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Exelixis Clinical Site #5

Myrtle Beach, South Carolina, 29572, United States

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Exelixis Clinical Site #10

Nashville, Tennessee, 37203, United States

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Exelixis Clinical Site #38

Nashville, Tennessee, 37232, United States

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Exelixis Clinical Site #64

Fairfax, Virginia, 22031, United States

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Exelixis Clinical Site #57

Seattle, Washington, 98109, United States

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Exelixis Clinical Site #1

Spokane, Washington, 99208, United States

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Exelixis Clinical Site #13

Madison, Wisconsin, 53792, United States

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Exelixis Clinical Site #153

Pilar, Buenos Aires, B1629ODT, Argentina

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Exelixis Clinical Site #109

Rosario, Santa Fe Province, S2000KZE, Argentina

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Exelixis Clinical Site #73

San Miguel de Tucumán, Tucumán Province, T4000, Argentina

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Exelixis Clinical Site #54

Buenos Aires, C1125ABD, Argentina

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Exelixis Clinical Site #63

CABA, C1120AAT, Argentina

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Exelixis Clinical Site #110

Ciudad Autonoma de Buenos Aire, C1426ANZ, Argentina

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Exelixis Clinical Site #120

Córdoba, X5004, Argentina

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Exelixis Clinical Site #32

Albury, New South Wales, 2640, Australia

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Exelixis Clinical Site #35

Kogarah, New South Wales, 2217, Australia

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Exelixis Clinical Site #27

North Ryde, New South Wales, 2109, Australia

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Exelixis Clinical Site #33

Sydney, New South Wales, 2065, Australia

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Exelixis Clinical Site #17

South Brisbane, Queensland, 4101, Australia

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Exelixis Clinical Site #14

Woolloongabba, Queensland, 4102, Australia

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Exelixis Clinical Site #18

Adelaide, South Australia, 5000, Australia

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Exelixis Clinical Site #11

North Adelaide, South Australia, 5006, Australia

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Exelixis Clinical Site #9

Ballarat, Victoria, 3350, Australia

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Exelixis Clinical Site #23

Box Hill, Victoria, 3128, Australia

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Exelixis Clinical Site #26

Subiaco, Western Australia, 6008, Australia

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Exelixis Clinical Site #98

Wiener Neustadt, Lower Austria, 2700, Austria

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Exelixis Clinical Site #76

Linz, Upper Austria, 4020, Austria

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Exelixis Clinical Site #75

Salzburg, 5020, Austria

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Exelixis Clinical Site #126

Vienna, 1090, Austria

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Exelixis Clinical Site #112

Brussels, 1000, Belgium

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Exelixis Clinical Site #146

Hasselt, 3500, Belgium

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Exelixis Clinical Site #154

Belo Horizonte, Minas Gerais, 30130-090, Brazil

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Exelixis Clinical Site #155

Curitiba, Paraná, 80530-010, Brazil

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Exelixis Clinical Site #158

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

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Exelixis Clinical Site #140

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

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Exelixis Clinical Site #163

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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Exelixis Clinical Site #168

Barretos, São Paulo, 14784-400, Brazil

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Exelixis Clinical Site #162

São José do Rio Preto, São Paulo, 15090-000, Brazil

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Exelixis Clinical Site #119

São Paulo, 01323-001, Brazil

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Exelixis Clinical Site #141

São Paulo, 01327-001, Brazil

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Exelixis Clinical Site #22

Calgary, Alberta, T2N 4N2, Canada

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Exelixis Clinical Site #105

Winnipeg, Manitoba, R3E 0V9, Canada

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Exelixis Clinical Site #46

Ottawa, Ontario, K1H 8L6, Canada

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Exelixis Clinical Site #25

Toronto, Ontario, M4N 3M5, Canada

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Exelixis Clinical Site #113

Montreal, Quebec, H3T 1E2, Canada

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Exelixis Clinical Site #85

Temuco, Región de La Araucanía (IX), 4810561, Chile

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Exelixis Clinical Site #91

Santiago, 7500921, Chile

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Exelixis Clinical Site #100

Santiago, 8420383, Chile

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Exelixis Clinical Site #89

Králová, 50005, Czechia

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Exelixis Clinical Site #114

Prague, 140 59, Czechia

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Exelixis Clinical Site #118

Prague, 150 06, Czechia

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Exelixis Clinical Site #50

Helsinki, 00029, Finland

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Exelixis Clinical Site #56

Tampere, 33520, Finland

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Exelixis Clinical Site #52

Turku, 20520, Finland

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Exelixis Clinical Site #86

Bordeaux, 33075, France

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Exelixis Clinical Site #71

Le Mans, 72000, France

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Exelixis Clinical Site #78

Lyon, 69373, France

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Exelixis Clinical Site #80

Montpellier, 34295, France

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Exelixis Clinical Site #66

Nice, 06189, France

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Exelixis Clinical Site #150

Paris, 75015, France

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Exelixis Clinical Site #65

Reims, 51726, France

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Exelixis Clinical Site #125

Rennes, 35042, France

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Exelixis Clinical Site #128

Strasbourg, 67000, France

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Exelixis Clinical Site #90

Strasbourg, 67200, France

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Exelixis Clinical Site #42

Toulouse, 31059, France

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Exelixis Clinical Site #67

Vandœuvre-lès-Nancy, 54519, France

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Exelixis Clinical Site #37

Villejuif, 94800, France

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Exelixis Clinical Site #127

Heidelberg, Baden-Wurttemberg, 69120, Germany

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Exelixis Clinical Site #115

Tübingen, Baden-Wurttemberg, 72076, Germany

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Exelixis Clinical Site #117

Frankfurt am Main, Hesse, 60596, Germany

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Exelixis Clinical Site #139

Münster, North Rhine-Westphalia, 48149, Germany

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Exelixis Clinical Site #171

Münster, North Rhine-Westphalia, 90419, Germany

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Exelixis Clinical Site #164

Mainz, Rhineland-Palatinate, 55131, Germany

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Exelixis Clinical Site #137

Jena, Thuringia, 077477, Germany

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Exelixis Clinical Site #124

Dresden, 01307, Germany

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Exelixis Clinical Site #28

Hong Kong, Hong Kong

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Exelixis Clinical Site #136

Shatin, Hong Kong

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Exelixis Clinical Site #111

Tuenmen, Hong Kong

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Exelixis Clinical Site #39

Budapest, 1122, Hungary

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Exelixis Clinical Site #51

Pécs, 7624, Hungary

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Exelixis Clinical Site #88

Beersheba, 84101, Israel

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Exelixis Clinical Site #81

Haifa, 3109601, Israel

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Exelixis Clinical Site #84

Jerusalem, 9112001, Israel

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Exelixis Clinical Site #121

Kfar Saba, 4428164, Israel

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Exelixis Clinical Site #97

Petah Tikva, 49100, Israel

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Exelixis Clincal Site #129

Ramat Gan, 5265601, Israel

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Exelixis Clinical Site #41

Meldola, Forli - Cesena, 47014, Italy

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Exelixis Clinical Site #70

Faenza, Ravenna, 48018, Italy

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Exelixis Clinical Site #47

Arezzo, 52100, Italy

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Exelixis Clinical Site #60

Modena, 41124, Italy

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Exelixis Clinical Site #61

Padua, 35128, Italy

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Exelixis Clinical Site #59

Pavia, 27100, Italy

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Exelixis Clinical Site #104

Perugia, 06132, Italy

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Exelixis Clinical Site #68

Terni, 05100, Italy

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Exelixis Clinical Site #123

Aguascalientes, Aguascalientes, 20116, Mexico

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Exelixis Clinical Site #167

León, Guanajuato, 37000, Mexico

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Exelixis Clinical Site #169

Zapopan, Jalisco, 45070, Mexico

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Exelixis Clinical Site #134

Monterrey, Nuevo León, 64710, Mexico

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Exelixis Clinical Site #132

Oaxaca City, Oaxaca, 68000, Mexico

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Exelixis Clinical Site #160

Mexico City, 03100, Mexico

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Exelixis Clinical Site #131

Querétaro, 76000, Mexico

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Exelixis Clinical Site #161

Querétaro, 76090, Mexico

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Exelixis Clinical Site #144

Amsterdam, 1105 AZ, Netherlands

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Exelixis Clinical Site #149

Rotterdam, 3015 GD, Netherlands

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Exelixis Clinical Site #122

Hamilton, Waikato Region, 3204, New Zealand

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Exelixis Clinical Site #148

Newtown, Wellington Region, 6021, New Zealand

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Exelixis Clinical Site #31

Biała Podlaska, 21-500, Poland

Location

Exelixis Clinical Site #62

Bydgoszcz, 85-796, Poland

Location

Exelixis Clinical Site #135

Gdansk, 80-219, Poland

Location

Exelixis Clinical Site #99

Otwock, 05-400, Poland

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Exelixis Clinical Site #83

Poznan, 60-693, Poland

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Exelixis Clinical Site #77

Singapore, 119074, Singapore

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Exelixis Clinical Site #40

Singapore, 169610, Singapore

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Exelixis Clinical Site #147

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Exelixis Clinical Site #143

Seoul, 03722, South Korea

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Exelixis Clinical Site #151

Seoul, 05505, South Korea

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Exelixis Clinical Site #152

Seoul, 06351, South Korea

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Exelixis Clinical Site #53

Santiago de Compostela, Coruña, 15706, Spain

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Exelixis Clinical Site #45

Pamplona, Navarre, 31008, Spain

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Exelixis Clinical Site #43

Barcelona, 08035, Spain

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Exelixis Clinical Site #36

Barcelona, 08036, Spain

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Exelixis Clinical Site #49

Córdoba, 14004, Spain

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Exelixis Clinical Site #34

Madrid, 28009, Spain

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Exelixis Clinical Site #94

Madrid, 28040, Spain

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Exelixis Clinical Site #20

Madrid, 28041, Spain

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Exelixis Clinical Site #55

Madrid, 28050, Spain

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Exelixis Clinical Site #96

Oviedo, 33011, Spain

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Exelixis Clinical Site #74

Valencia, 46009, Spain

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Exelixis Clinical Site #142

Taichung, 404, Taiwan

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Exelixis Clinical Site #138

Taipei, 10002, Taiwan

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Exelixis Clinical Site #173

Taoyuan District, 333, Taiwan

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Exelixis Clinical Site #72

Cambridge, CB2 0QQ, United Kingdom

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Exelixis Clinical Site #93

Glasgow, G12 0YN, United Kingdom

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Exelixis Clinical Site #30

London, EC1A 7BE, United Kingdom

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Exelixis Clinical Site #172

London, W6 8RF, United Kingdom

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Exelixis Clinical Site #92

Manchester, M20 4BX, United Kingdom

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Related Publications (4)

• 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.

  PMID: 37163623 DERIVED

• Labriola 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.

  PMID: 35383907 DERIVED

• Mar 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.

  PMID: 34550754 DERIVED

• Hofmann 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.

  PMID: 33058158 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms; Carcinoma

Interventions

cabozantinib; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio.

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: May 3, 2019
• Study Start: June 25, 2019
• Primary Completion: January 31, 2022
• Study Completion (Estimated): January 31, 2027
• Last Updated: September 10, 2025
• Results First Posted: September 10, 2025

Record last verified: 2025-08

Locations

NZ (2); TW (3); AR (7); PL (5); ES (11); KR (4); US (30); ME (8); SG (2); HU (2); CA (5); GB (5); DE (8); CZ (3); AU (4); BE (2); BR (9); FR (13); IL (6); FI (3); IT (8); CL (3); HK (3); NL (2)