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

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ClinicalTrials.gov Identifier: NCT03937219
Recruitment Status : Active, not recruiting
First Posted : May 3, 2019
Last Update Posted : April 13, 2023
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Description
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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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Cabozantinib Biological: Nivolumab Biological: Ipilimumab Drug: Cabozantinib-matched placebo Phase 3

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 840 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : June 25, 2019
Actual Primary Completion Date : January 31, 2022
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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:
  • Opdivo
  • BMS-936558

Biological: Ipilimumab
Specified dose on specified days.
Other Names:
  • Yervoy
  • BMS-734016
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:
  • Opdivo
  • BMS-936558

Biological: Ipilimumab
Specified dose on specified days.
Other Names:
  • Yervoy
  • BMS-734016

Drug: Cabozantinib-matched placebo
Specified dose on specified days.


Outcome Measures
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Primary Outcome Measures :
  1. Duration of Progression-Free Survival (PFS) per RECIST 1.1 as determined by blinded independent radiology committee (BIRC) [ Time Frame: Up to 23 months after first subject randomized ]

Secondary Outcome Measures :
  1. Duration of Overall Survival (OS) [ Time Frame: Up to 69 months after first subject randomized ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03937219


Locations
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Sponsors and Collaborators
Exelixis
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT03937219    
Other Study ID Numbers: XL184-313
First Posted: May 3, 2019    Key Record Dates
Last Update Posted: April 13, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Exelixis:
renal
cancer
carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
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
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action