A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)
Condition: Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: bempegaldesleukin; sunitinib; nivolumab; cabozantinib
Intervention description: Specified dose on specified days; Specified dose on specified days; Specified dose on specified days; Specified dose on specified days
Intervention MeSH terms: Nivolumab; Sunitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 623.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Cancer; Kidney Neoplasms; Renal Cancer; Renal Neoplasms; CD122; CD122-Biased Agonist; CD122-Biased Cytokine; IL-2 receptor agonist; Immuno-oncology therapy; NKTR-214; Nivolumab; Opdivo®; PD-L1; PD-1; Bempegaldesleukin; IL-2; BEMPEG; CD122-Preferential; IL-2 pathway agonist; Checkpoint inhibition; Immune checkpoint inhibitor

Summary:

      The main purpose of this study is to compare the objective response rate (ORR) and overall
      survival (OS) of bempegaldesleukin (NKTR-214: BEMPEG) combined with nivolumab to that of
      tyrosine kinase inhibitor (TKI) monotherapy (sunitinib or cabozantinib) in IMDC intermediate-
      or poor-risk patients and IMDC all-risk patients with previously untreated advanced renal
      cell carcinoma (RCC).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Provide written, informed consent to participate in the study and follow the study
             procedures

          -  Karnofsky Performance Status (KPS) of at least 70%

          -  Measurable disease per mRECIST 1.1 criteria

          -  Histologically confirmed RCC with a clear-cell component (may have sarcomatoid
             features); advanced (not amenable to curative surgery or radiation therapy) or
             metastatic (AJCC Stage IV) RCC

          -  Patients with any International Metastatic Renal Cell Carcinoma Database Consortium
             (IMDC) score (favorable-, intermediate-, or poor-risk) are eligible. At least one IMDC
             prognostic factor must be present to qualify as either intermediate- or poor-risk
             renal cell carcinoma.

          -  No prior systemic therapy (including neoadjuvant, adjuvant, or vaccine therapy) for
             RCC

        Key Exclusion Criteria:

          -  An active, known or suspected autoimmune disease that has required systemic treatment
             within the past 3 months (exceptions exist)

          -  Patients who have a known additional malignancy that is progressing or requires active
             treatment (exceptions exist)

          -  Any tumor invading the wall of a major blood vessels

          -  Any tumor invading the gastrointestinal (GI) tract or any evidence of endotracheal or
             endobronchial tumor within 28 days prior to randomization

          -  Need for >2 medications for management of hypertension (including diuretics)

          -  History of pulmonary embolism, deep vein thrombosis (not including tumor thrombus), or
             clinically significant thromboembolic event within 3 months of randomization

        Additional protocol defined inclusion/exclusion criteria and exceptions apply