A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 194
- Locations
- 14
- Primary Endpoint
- Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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
Arms & Interventions
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
Intervention: Nivolumab (Biological)
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
Intervention: Sunitinib (Drug)
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
Intervention: Nivolumab (Biological)
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
Intervention: Pazopanib (Biological)
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
Intervention: Nivolumab (Biological)
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
Intervention: Ipilimumab (Biological)
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
Intervention: Nivolumab (Biological)
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
Intervention: Ipilimumab (Biological)
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
Intervention: Nivolumab (Biological)
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
Intervention: Ipilimumab (Biological)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Rate of Progression-free Survival (PFS) at Week 24(24 weeks)
- 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))
- 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))
- 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))