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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Clear-cell Metastatic Renal Cell Carcinoma; Renal Cell Carcinoma

Treatments: Drug: Sunitinib; Biological: Nivolumab; Biological: Pazopanib; Biological: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01472081

CA209-016

Details and patient eligibility

About

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.

Enrollment: 194 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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194 participants in 5 patient groups

Arm S: Nivolumab + Sunitinib

Experimental group

Description:

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

Treatment:

Biological: Nivolumab

Drug: Sunitinib

Arm P: Nivolumab + Pazopanib

Experimental group

Description:

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

Treatment:

Biological: Pazopanib

Biological: Nivolumab

Arm I-1: Nivolumab + Ipilimumab

Experimental group

Description:

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

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Arm I-3: Nivolumab + Ipilimumab

Experimental group

Description:

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

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Arm IN-3: Nivolumab+Ipilimumab

Experimental group

Description:

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

Treatment:

Biological: Ipilimumab

Biological: Nivolumab