Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
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| ClinicalTrials.gov Identifier: NCT01472081 |
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Recruitment Status :
Completed
First Posted : November 16, 2011
Results First Posted : August 2, 2019
Last Update Posted : December 2, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Cell Carcinoma Clear-cell Metastatic Renal Cell Carcinoma | Biological: Nivolumab Biological: Pazopanib Drug: Sunitinib Biological: Ipilimumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 194 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma |
| Actual Study Start Date : | February 9, 2012 |
| Actual Primary Completion Date : | February 2, 2016 |
| Actual Study Completion Date : | June 3, 2021 |
| Arm | Intervention/treatment |
|---|---|
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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 Name: BMS-936558 (MDX-1106) Drug: Sunitinib Other Names:
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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 Name: BMS-936558 (MDX-1106) Biological: Pazopanib Other Name: Votrient (Pazopanib hydrochloride) |
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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 Name: BMS-936558 (MDX-1106) Biological: Ipilimumab Other Name: YERVOY™ |
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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 Name: BMS-936558 (MDX-1106) Biological: Ipilimumab Other Name: YERVOY™ |
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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 Name: BMS-936558 (MDX-1106) Biological: Ipilimumab Other Name: YERVOY™ |
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
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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
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
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): NCT01472081
| United States, California | |
| City Of Hope | |
| Duarte, California, United States, 91010-3000 | |
| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins | |
| Baltimore, Maryland, United States, 21287 | |
| United States, Massachusetts | |
| Beth Israel Deaconess Medical Center | |
| Boston, Massachusetts, United States, 02215 | |
| United States, New Hampshire | |
| Dartmouth-Hitchcock Medical Center | |
| Lebanon, New Hampshire, United States, 03756 | |
| United States, New York | |
| Memorial Sloan Kettering Nassau | |
| New York, New York, United States, 10065 | |
| United States, North Carolina | |
| Blumenthal Cancer Center | |
| Charlotte, North Carolina, United States, 28204 | |
| United States, Ohio | |
| Cleveland Clinic | |
| Cleveland, Ohio, United States, 44195 | |
| United States, Pennsylvania | |
| Fox Chase Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19111 | |
| United States, Tennessee | |
| Tennessee Oncology, PLLC | |
| Nashville, Tennessee, United States, 37203 | |
| United States, Texas | |
| University Of Texas M.D. Anderson Cancer Center | |
| Houston, Texas, United States, 77030-4009 | |
| Canada, Alberta | |
| Tom Baker Cancer Centre | |
| Calgary, Alberta, Canada, T2N 4N2 | |
| Cross Cancer Institute | |
| Edmonton, Alberta, Canada, T6G 1Z2 | |
| Canada, British Columbia | |
| BC Cancer Agency - Vancouver Centre | |
| Vancouver, British Columbia, Canada, V5Z 4E6 | |
| Canada, Ontario | |
| Princess Margaret Cancer Centre | |
| Toronto, Ontario, Canada, M5G 1Z5 | |
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01472081 |
| Other Study ID Numbers: |
CA209-016 |
| First Posted: | November 16, 2011 Key Record Dates |
| Results First Posted: | August 2, 2019 |
| Last Update Posted: | December 2, 2021 |
| Last Verified: | November 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 Kidney Diseases Urologic Diseases Nivolumab |
Ipilimumab Sunitinib Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors |