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

Conditions: Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma

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

Registration Number: NCT03729245

Lead Sponsor: Nektar Therapeutics

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 623

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

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.

Trial Locations

Locations (95): Alaska Urological
🇺🇸
Anchorage, Alaska, United States
CARTI Cancer Center
🇺🇸
Little Rock, Arkansas, United States
Centro de Investigación Pergamino S.A
🇦🇷
Buenos Aires, Argentina
Tulane Medical Center
🇺🇸
New Orleans, Louisiana, United States
Huntsman Cancer Hospital - PPDS
🇺🇸
Salt Lake City, Utah, United States
Adelaide Cancer Centre
🇦🇺
Kurralta Park, South Australia, Australia
Centro Oncologico Riojano Integral (cori)
🇦🇷
La Rioja, Argentina
Hospital Provincial Del Centenario
🇦🇷
Rosario, Argentina
Centro Médico Austral
🇦🇷
Buenos Aires, Argentina
Liga Norte Riograndense Contra O Cancer
🇧🇷
Natal, Rio Grande Do Norte, Brazil
Instituto Médico Especializado Alexander Fleming
🇦🇷
Buenos Aires, Argentina
Centro Médico Privado CEMAIC
🇦🇷
Córdoba, Argentina
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Oncovida
🇨🇱
Santiago, Chile
Barwon Health
🇦🇺
Parkville, Victoria, Australia
Sanatorio Privado Duarte Quirós, de Clínica Colombo S.A.
🇦🇷
Córdoba, Argentina
Centro de Investigación Clínica - Clínica Viedma
🇦🇷
Viedma, Rio Negro, Argentina
Hospital Mae de Deus
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Royal North Shore Hospital
🇦🇺
Saint Leonards, New South Wales, Australia
Macquarie University
🇦🇺
Sydney, New South Wales, Australia
Clinica Santa Maria
🇨🇱
Santiago, Chile
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
🇧🇷
Curitiba, Parana, Brazil
Altay Regional Oncology Center
🇷🇺
Barnaul, Russian Federation
Winship Cancer Institute, Emory University
🇺🇸
Atlanta, Georgia, United States
University of Maryland Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
Centro de Oncologia Da Bahia
🇧🇷
Salvador, Bahia, Brazil
Universidade Federal do Rio Grande do Sul - UFRGS
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Oncocentro, Belo Horizonte
🇧🇷
Belo Horizonte, Minas Gerais, Brazil
Associação Hospital de Caridade Ijuí
🇧🇷
Ijuí, Rio Grande Do Sul, Brazil
Clínica de Oncologia de Porto Alegre SS Ltda
🇧🇷
Rio Grande, Rio Grande Do Sul, Brazil
Hospital Bruno Born
🇧🇷
Lajeado, Rio Grande Do Sul, Brazil
Ensino E Terapia de Inovação Clínica Assistência Multidiciplinar Em Oncologia Ética
🇧🇷
Salvador, Bahia, Brazil
Irmandade Da Santa Casa de Misericordia de Porto Alegre
🇧🇷
Porto Alegre, Rio Grande Do Sul, Brazil
Cenantron - Centro Avancado de Tratamento Oncologico Ltda
🇧🇷
Belo Horizonte, Minas Gerais, Brazil
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Health Pharma Professional Research S.A de C.V.
🇲🇽
Ciudad de Mexico, Distrito Federal, Mexico
Instituto Joinvilense de Hematologia E Oncologia
🇧🇷
Joinville, Santa Catarina, Brazil
University of Miami
🇺🇸
Miami, Florida, United States
Centro Investigacion Clinica Del Sur
🇨🇱
Temuco, Chile
Hospital Amaral Carvalho
🇧🇷
Jaú, São Paulo, Brazil
Axis Heilsa S. De R.L. de C.V.
🇲🇽
Monterrey, Nuevo León, Mexico
Oncocentro APYS
🇨🇱
Viña Del Mar, Chile
Centro de Investigaciones Clínicas Vina del Mar
🇨🇱
Viña Del Mar, Chile
Accelerium, S. de R.L. de C.V.
🇲🇽
Monterrey, Mexico
ONCOCARE S.A.C. (Clinica Aliada)
🇵🇪
Lima, Peru
Sanatorio Parque de Rosario
🇦🇷
Santa Fe, Argentina
Sanatorio Allende S.A.
🇦🇷
Córdoba, Argentina
Instituto de Pesquisas Clínicas Para Estudos Multicêntricos
🇧🇷
Caxias Do Sul, Brazil
Federal State Institution Medical Radiology Research Center
🇷🇺
Obninsk, Russian Federation
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Instituto COI de Pesquisa, Educação e Gestão
🇧🇷
Rio De Janeiro, Brazil
Fundação Antônio Prudente - AC Camargo Câncer Center
🇧🇷
São Paulo, Brazil
Hospital Santa Marcelina
🇧🇷
São Paulo, Brazil
Auckland City Hospital
🇳🇿
Auckland, New Zealand
Clinical Oncology Dispensary
🇷🇺
Omsk, Russian Federation
Hospital Orkli LLC
🇷🇺
Saint Petersburg, Russian Federation
Western Regional Medical Center - CTCA - PPDS
🇺🇸
Goodyear, Arizona, United States
University of California Irvine
🇺🇸
Orange, California, United States
Innovative Clinical Research Institute
🇺🇸
Whittier, California, United States
North Shore Hematology Oncology Association PC
🇺🇸
Port Jefferson Station, New York, United States
Eastern Regional Medical Center - CTCA
🇺🇸
Philadelphia, Pennsylvania, United States
Lehigh Valley Physician Group (LVPG) - Hematology Oncology
🇺🇸
Allentown, Pennsylvania, United States
Providence Cancer Institute, Franz Clinic
🇺🇸
Portland, Oregon, United States
Penn State Milton S Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Fundación Arturo López Pérez (FALP) - PPDS
🇨🇱
Santiago, Chile
CAIPO Centro para la atención integral del paciente oncológico
🇦🇷
San Miguel De Tucumán, Argentina
Orange Cancer Centre
🇦🇺
Orange, New South Wales, Australia
Fundação Pio XII Hospital de Câncer de Barretos
🇧🇷
Barretos, Sao Paulo, Brazil
Hospital das Clinicas - UNICAMP
🇧🇷
Campinas, Sao Paulo, Brazil
Fundação do ABC - Faculdade de Medicina do ABC
🇧🇷
Santo André, Sao Paulo, Brazil
Instituto Do Câncer Do Ceará ICC
🇧🇷
Fortaleza, Brazil
Animi
🇧🇷
Lages, Brazil
Instituto Nacional de Câncer
🇧🇷
Rio De Janeiro, Brazil
Hospital Alemão Oswaldo Cruz
🇧🇷
São Paulo, Brazil
Hospital de Base Da Faculdade de Medicina de São José Do Rio Preto
🇧🇷
São José Do Rio Preto, Brazil
Corporacion de Beneficencia Osorno
🇨🇱
Osorno, Los Lagos, Chile
Clinical Research Chile SpA
🇨🇱
Valdivia, Los Rios, Chile
Centro de Investigacion Clinica Chapultepec S.A. de C.V.
🇲🇽
Morelia, Michoacan, Mexico
Unidad Médica Onco-Hematológica
🇲🇽
Puebla, Mexico
Clinica Internacional S.A. - Sede San Borja
🇵🇪
Lima, Peru
Hospital Nacional Cayetano Heredia
🇵🇪
Lima, Peru
Clinica Peruana Americana
🇵🇪
Trujillo, La Lobertad, Peru
Chelyabinsk Regional Clinical Oncology Dispensary
🇷🇺
Chelyabinsk, Russian Federation
LLC Evimed
🇷🇺
Chelyabinsk, Russian Federation
Kursk Regional Oncology Centre
🇷🇺
Kursk, Russian Federation
Central Clinical Hospital With Polyclinic of President Administration of RF
🇷🇺
Moscow, Russian Federation
PMI Euromedservice
🇷🇺
Pushkin, Russian Federation
State Institution of Healthcare "Volgograd Regional Urology and Nephrology Centre"
🇷🇺
Volzhskiy, Russian Federation
Railway Clinical Hospital JSC RZhD
🇷🇺
Saint Petersburg, Russian Federation
Regional Clinical Oncology Hospital
🇷🇺
Yaroslavl, Russian Federation
National Cancer Centre
🇸🇬
Singapore, Singapore
Oncocare Cancer Centre
🇸🇬
Singapore, Singapore
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States