Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)

November 30, 2021 updated by: Bristol-Myers Squibb

A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

194

Phase

  • Phase 1

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

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer Agency - Vancouver Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 1Z5
        • Princess Margaret Cancer Centre
  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Blumenthal Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Texas
      • Houston, Texas, United States, 77030-4009
        • University of Texas M.D. Anderson Cancer Center

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

Genders Eligible for Study

All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • 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:

    1. 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
    2. Only prior cytokine based treatment for metastatic RCC [eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)] as prior therapy is allowed

Exclusion Criteria:

  • 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)

Exclusion Criteria for Arm S and Arm P only:

  • 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
  • Active bleeding or bleeding susceptibility

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: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm S: Nivolumab + Sunitinib

Nivolumab 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
Biological: Nivolumab
Other Names:
  • BMS-936558 (MDX-1106)
Drug: Sunitinib
Other Names:
  • Sunitinib Malate
  • Sutent®
EXPERIMENTAL: Arm P: Nivolumab + Pazopanib

Nivolumab 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
Biological: Nivolumab
Other Names:
  • BMS-936558 (MDX-1106)
Biological: Pazopanib
Other Names:
  • Votrient (Pazopanib hydrochloride)
EXPERIMENTAL: Arm I-1: Nivolumab + Ipilimumab

Nivolumab 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
Biological: Nivolumab
Other Names:
  • BMS-936558 (MDX-1106)
Biological: Ipilimumab
Other Names:
  • YERVOY™
EXPERIMENTAL: Arm I-3: Nivolumab + Ipilimumab

Nivolumab 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
Biological: Nivolumab
Other Names:
  • BMS-936558 (MDX-1106)
Biological: Ipilimumab
Other Names:
  • YERVOY™
EXPERIMENTAL: Arm IN-3: Nivolumab+Ipilimumab

Nivolumab 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
Biological: Nivolumab
Other Names:
  • BMS-936558 (MDX-1106)
Biological: Ipilimumab
Other Names:
  • YERVOY™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation
Time Frame: From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response Rate (BOR)
Time Frame: 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)

BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first.

CR = Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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)
Time Frame: From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)

ORR was defined as the proportion of participants who achieved a BOR of either complete response (CR) or partial response (PR) in the population of interest.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)
Duration of Response (DOR)
Time Frame: From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
DOR was computed for participants with BOR of CR or PR only, and defined as the time between the date of first documented objective response and the date of the first subsequent disease progression or death. Participants who remained alive and had not progressed were censored on the last tumor assessment date (prior to subsequent cancer therapy).
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
Time Frame: 24 weeks
Rate of PFS at week 24 was defined as the proportion of participants remaining progression free or surviving at 24 weeks, calculated by the product-limit method (Kaplan-Meier estimate) which took into account censored data. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
24 weeks
Progression-free Survival (PFS)
Time Frame: From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)
PFS was defined as the time from the date of first dose of study medication to the date of first disease progression or death. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)

Collaborators and Investigators

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

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharmaceutical Co. Ltd

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

Helpful Links

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)

February 9, 2012

Primary Completion (ACTUAL)

February 2, 2016

Study Completion (ACTUAL)

June 3, 2021

Study Registration Dates

First Submitted

October 26, 2011

First Submitted That Met QC Criteria

November 11, 2011

First Posted (ESTIMATE)

November 16, 2011

Study Record Updates

Last Update Posted (ACTUAL)

December 2, 2021

Last Update Submitted That Met QC Criteria

November 30, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-016

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.

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