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)

Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03729245
• Other study ID #: 17-214-09
• Secondary ID: CA045002
• Status: Terminated
• Phase: Phase 3
• Start date: December 18, 2018
• Est. completion date: October 19, 2022

Study information

• Verified date: March 2023
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Terminated
• Enrollment: 623
• Est. completion date: October 19, 2022
• Est. primary completion date: January 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma
• Renal Cell Carcinoma

Intervention

Biological:
• bempegaldesleukin
Specified dose on specified days

Drug:
• sunitinib
Specified dose on specified days

Biological:
• nivolumab
Specified dose on specified days

Drug:
• cabozantinib
Specified dose on specified days

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Nektar Therapeutics	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Chile,  Mexico,  New Zealand,  Peru,  Russian Federation,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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