Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma
1 other identifier
interventional
194
2 countries
14
Brief Summary
The purpose is to determine the safety, effectiveness and best dose to use when giving Nivolumab in combination with Sunitinib, Pazopanib, or Ipilimumab for the treatment of metastatic renal cell carcinoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2012
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2011
CompletedFirst Posted
Study publicly available on registry
November 16, 2011
CompletedStudy Start
First participant enrolled
February 9, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 2, 2016
CompletedResults Posted
Study results publicly available
August 2, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 3, 2021
CompletedDecember 2, 2021
November 1, 2021
4 years
October 26, 2011
May 23, 2018
November 30, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation
Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)
Secondary Outcomes (5)
Best Overall Response Rate (BOR)
From date of first dose to date of disease progression or subsequent anti-cancer therapy, whichever occurred first (assessed up to March 2016, approximately 49 months)
Objective Response Rate (ORR)
From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)
Duration of Response (DOR)
From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
Rate of Progression-free Survival (PFS) at Week 24
24 weeks
Progression-free Survival (PFS)
From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
Study Arms (5)
Arm S: Nivolumab + Sunitinib
EXPERIMENTALNivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Sunitinib 50 mg capsule by mouth on Days 1-28 of 42 day cycle until Progressive disease (PD), toxicity or discontinue for other reasons
Arm P: Nivolumab + Pazopanib
EXPERIMENTALNivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Pazopanib 800 mg tablet by mouth daily until Progressive disease (PD), toxicity or discontinue for other reasons
Arm I-1: Nivolumab + Ipilimumab
EXPERIMENTALNivolumab 3 mg/kg solution intravenously (IV) every 21 days during Induction phase and every 14 days during Maintenance phase until Progressive disease (PD), toxicity or discontinue for other reasons Ipilimumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase (Ipilimumab will not be administered during Maintenance phase) until Progressive disease (PD), toxicity or discontinue for other reasons
Arm I-3: Nivolumab + Ipilimumab
EXPERIMENTALNivolumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase
Arm IN-3: Nivolumab+Ipilimumab
EXPERIMENTALNivolumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase
Interventions
Eligibility Criteria
You may qualify if:
- Subjects with histological confirmation of RCC
- Advanced or metastatic disease
- Measurable disease as defined by RECIST 1.1 criteria
- Karnofsky Performance Status (KPS) ≥80%
- Available tumor tissue (archival or recent acquisition)
- Subjects enrolled in the I-1, I-3 expansion arms and IN-3 addition arms must not have received any prior systemic therapy for RCC with the following exceptions:
- One prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred ≥ 6 months after the last dose of the adjuvant or neoadjuvant therapy
- Only prior cytokine based treatment for metastatic RCC \[eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)\] as prior therapy is allowed
You may not qualify if:
- Active central nervous system (CNS) metastases
- Active or history of autoimmune disease
- Ongoing symptomatic cardiac dysrhythmias or uncontrolled atrial fibrillation
- History of cerebrovascular accident including transient ischemic attack within the past 12 months
- History of pulmonary embolism or deep vein thrombosis (DVT) within the past 6 months
- Chronic systemic steroids (\>10 mg/day Prednisone equivalents) or any other immunosuppressive agents
- White blood cell (WBC) \<2,000/mm3
- Neutrophiles \<1,500/mm3
- Platelets \<100,000/mm3
- Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x upper limit of normal (ULN)
- Total Bilirubin \>1.5x ULN (except subjects with Gilbert syndrome, total bilirubin \<3.0 mg/dL)
- Cardiac ejection fraction \<LLN (lower limit of normal)
- Serum creatinine \>1.5x ULN or creatinine clearance \<40 mL/min (Cockroft-Gault formula)
- For dose escalation cohorts - subjects who received prior Sunitinib or Pazopanib and required permanent discontinuation due to toxicity or required dose reduction or delay during the first 12 weeks of therapy due to toxicity, or received both prior Sunitinib and Pazopanib
- Poorly controlled hypertension
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bristol-Myers Squibblead
- Ono Pharmaceutical Co. Ltdcollaborator
Study Sites (14)
City Of Hope
Duarte, California, 91010-3000, United States
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
Baltimore, Maryland, 21287, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Memorial Sloan Kettering Nassau
New York, New York, 10065, United States
Blumenthal Cancer Center
Charlotte, North Carolina, 28204, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
University Of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030-4009, United States
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
BC Cancer Agency - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5, Canada
Related Publications (2)
Amin A, Plimack ER, Ernstoff MS, Lewis LD, Bauer TM, McDermott DF, Carducci M, Kollmannsberger C, Rini BI, Heng DYC, Knox J, Voss MH, Spratlin J, Berghorn E, Yang L, Hammers HJ. Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study. J Immunother Cancer. 2018 Oct 22;6(1):109. doi: 10.1186/s40425-018-0420-0.
PMID: 30348216DERIVEDDorff TB, Pal SK, Quinn DI. Novel tyrosine kinase inhibitors for renal cell carcinoma. Expert Rev Clin Pharmacol. 2014 Jan;7(1):67-73. doi: 10.1586/17512433.2014.862496. Epub 2013 Dec 2.
PMID: 24308791DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2011
First Posted
November 16, 2011
Study Start
February 9, 2012
Primary Completion
February 2, 2016
Study Completion
June 3, 2021
Last Updated
December 2, 2021
Results First Posted
August 2, 2019
Record last verified: 2021-11