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)

Phase 3

Terminated

Interventions: Biological: bempegaldesleukin
Drug: sunitinib
Biological: nivolumab
Drug: cabozantinib

Brief 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Combination of bempegaldesleukin + nivolumab	bempegaldesleukin	Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.
Combination of bempegaldesleukin + nivolumab	nivolumab	Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.
sunitinib or cabozantinib	sunitinib	Patients in Arm B will receive the Investigator's choice of either one of two treatment options.
sunitinib or cabozantinib	cabozantinib	Patients in Arm B will receive the Investigator's choice of either one of two treatment options.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC	Approximately 32 months	OS is defined as the time from date of first dose to the date of death from any cause. Patients without a date of death were censored at their last known alive date.
Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC	Approximately 32 months	ORR using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1 by Blinded Independent Central Review (BICR) in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) All-risk patients and intermediate- or poor-risk patients. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC	Approximately 32 months	Progression-free survival is defined as the time between the date of randomization and the first date of documented tumor progression using mRECIST 1.1 per BICR or death due to any cause, whichever comes first.

Locations (95): Alaska Urological
🇺🇸
Anchorage, Alaska, United States
Western Regional Medical Center - CTCA - PPDS
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Goodyear, Arizona, United States
CARTI Cancer Center
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Little Rock, Arkansas, United States
City of Hope National Medical Center
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Duarte, California, United States
University of California Irvine
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Orange, California, United States
Innovative Clinical Research Institute
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Whittier, California, United States
University of Miami
🇺🇸
Miami, Florida, United States
Winship Cancer Institute, Emory University
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Atlanta, Georgia, United States
Tulane Medical Center
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New Orleans, Louisiana, United States
University of Maryland Greenebaum Cancer Center
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Baltimore, Maryland, United States
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Alaska Urological
🇺🇸Anchorage, Alaska, United States