A Study to Compare Bempegaldesleukin (BEMPEG: NKTR-214) Combined With Nivolumab and Tyrosine Kinase Inhibitor (TKI) to Nivolumab and TKI Alone in Participants With Previously Untreated Kidney Cancer That is Advanced or Has Spread

Study Overview
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Brief Summary
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The purpose of this study is in Part 1, to determine the safety of nivolumab, bempegaldesleukin (BEMPEG: NKTR-214), and Tyrosine Kinase Inhibitor (TKI) combination.

Official Title
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A Phase 1 Study to Compare Bempegaldesleukin Combined With Nivolumab and Tyrosine Kinase Inhibitor (TKI) to Nivolumab and TKI Alone in Participants With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (mRCC) (PIVOT IO 011)

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: Nivolumab
* Drug: Axitinib
* Drug: Cabozantinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmation of renal cell carcinoma (RCC) with clear cell component including participants who may also have sarcomatoid features Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer (AJCC) Stage 4) RCC No prior systemic therapy, including prior PD-L1 therapy, for RCC is allowed with the following exception: i) One prior adjuvant or neoadjuvant therapy for completely resectable RCC is allowed. Therapy must have included an agent that targets vascular endothelial growth factor (VEGF) pathway or VEGF receptors and recurrence must have occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy Life Expectancy ≥ 12 weeks Karnofsky Performance Status (KPS) of at least 70% Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria Males and females must agree to follow specific methods of contraception, if applicable Exclusion Criteria: Active CNS brain metastases or leptomeningeal metastases Active, known or suspected autoimmune disease Inadequately treated adrenal insufficiency History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA/TIA arterial thromboembolic event (eg, internal jugular vein thrombosis) within 3 months prior to treatment assignment (Part 1) and randomization (Part 2) Other protocol-defined inclusion/exclusion criteria 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A (Part 1): Nivolumab + Axitinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: OPDIVO;Drug: Axitinib<br>* Specified dose on specified days<br>* Other names: INLYTA;|
| Experimental: Part 1B (Part 1): Nivolumab + Cabozantinib<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: OPDIVO;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 |
| --- | --- | --- |
| Incidence of adverse events (AEs) by severity (Part 1) |  | Up to 2.5 years | 
| Incidence of serious adverse events (SAEs) (Part 1) |  | Up to 2.5 years | 
| Incidence of dose-limiting toxicities (DLTs) (Part 1) |  | Up to 2.5 years | 
| Incidence of AEs leading to discontinuation (Part 1) |  | Up to 5 years | 
| Incidence of immune-mediated adverse events (imAEs) (Part 1) |  | Up to 5 years | 
| Incidence of changes in clinical laboratory results by severity: Hematology tests (Part 1) |  | Up to 2.5 years | 
| Incidence of changes in clinical laboratory results by severity: Clinical Chemistry tests (Part 1) |  | Up to 2.5 years | 
| Incidence of changes in clinical laboratory results by severity: Urinalysis tests (Part 1) |  | Up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NKTR-214, nivolumab, bempeg