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)

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 3 Randomized Open Label Study to Compare NKTR-214 Combined With Nivolumab to the Investigator's Choice of Sunitinib or Cabozantinib in Patients With Previously Untreated Advanced Renal Cell Carcinoma

Conditions
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Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Biological: bempegaldesleukin
* Drug: sunitinib
* Biological: nivolumab
* Drug: cabozantinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination of bempegaldesleukin + nivolumab<br>Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. | Biological: bempegaldesleukin<br>* Specified dose on specified days<br>* Other names: BMS-986321;Biological: nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Active Comparator: sunitinib or cabozantinib<br>Patients in Arm B will receive the Investigator's choice of either one of two treatment options. | Drug: sunitinib<br>* Specified dose on specified days<br>* Other names: Sutent®;Drug: cabozantinib<br>* Specified dose on specified days<br>* Other names: Cabometyx®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Approximately 32 months | 
| Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC | 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. | Approximately 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Approximately 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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