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)

NCT03729245 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 17-214-09CA045002
• Study Type: interventional
• Target: 623
• Locations: 10 countries
• Sites: 96

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).

Conditions

Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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

Study Arms (2)

Combination of bempegaldesleukin + nivolumab

EXPERIMENTAL

Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.

Biological: bempegaldesleukin; Biological: nivolumab

sunitinib or cabozantinib

ACTIVE COMPARATOR

Patients in Arm B will receive the Investigator's choice of either one of two treatment options.

Drug: sunitinib; Drug: cabozantinib

Interventions

bempegaldesleukin BIOLOGICAL

Specified dose on specified days

Also known as: BEMPEG, BMS-986321

Combination of bempegaldesleukin + nivolumab

sunitinib DRUG

Specified dose on specified days

Also known as: Sutent®

sunitinib or cabozantinib

nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo®, BMS-936558

Combination of bempegaldesleukin + nivolumab

cabozantinib DRUG

Specified dose on specified days

Also known as: Cabometyx®

sunitinib or cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nektar Therapeutics: lead
• Bristol-Myers Squibb: collaborator

Study Sites (96)

Alaska Urological

Anchorage, Alaska, 99503, United States

Location

Western Regional Medical Center - CTCA - PPDS

Goodyear, Arizona, 85338, United States

Location

CARTI Cancer Center

Little Rock, Arkansas, 72205, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89106, United States

Location

North Shore Hematology Oncology Association PC

Port Jefferson Station, New York, 11776, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Providence Cancer Institute, Franz Clinic

Portland, Oregon, 97213, United States

Location

Lehigh Valley Physician Group (LVPG) - Hematology Oncology

Allentown, Pennsylvania, 18103, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Eastern Regional Medical Center - CTCA

Philadelphia, Pennsylvania, 19124, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Hospital - PPDS

Salt Lake City, Utah, 84112, United States

Location

Centro de Investigación Clínica - Clínica Viedma

Viedma, Río Negro Province, R8500ACE, Argentina

Location

Centro de Investigación Pergamino S.A

Buenos Aires, 2700, Argentina

Location

Centro Médico Austral

Buenos Aires, C1019ABS, Argentina

Location

Instituto Médico Especializado Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Centro Médico Privado CEMAIC

Córdoba, X5000HHW, Argentina

Location

Sanatorio Allende S.A.

Córdoba, X5000JHQ, Argentina

Location

Sanatorio Privado Duarte Quirós, de Clínica Colombo S.A.

Córdoba, X5002AOQ, Argentina

Location

Centro Oncologico Riojano Integral (cori)

La Rioja, F5300COE, Argentina

Location

Hospital Provincial Del Centenario

Rosario, S2002KDS, Argentina

Location

CAIPO Centro para la atención integral del paciente oncológico

San Miguel de Tucumán, 4000, Argentina

Location

Sanatorio Parque de Rosario

Santa Fe, S2000DSV, Argentina

Location

Orange Cancer Centre

Orange, New South Wales, 2800, Australia

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Macquarie University

Sydney, New South Wales, 2109, Australia

Location

Adelaide Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Barwon Health

Parkville, Victoria, 3050, Australia

Location

Centro de Oncologia Da Bahia

Salvador, Estado de Bahia, 41820-021, Brazil

Location

Ensino E Terapia de Inovação Clínica Assistência Multidiciplinar Em Oncologia Ética

Salvador, Estado de Bahia, 41950-610, Brazil

Location

Cenantron - Centro Avancado de Tratamento Oncologico Ltda

Belo Horizonte, Minas Gerais, 30190-130, Brazil

Location

Oncocentro, Belo Horizonte

Belo Horizonte, Minas Gerais, 30360-680, Brazil

Location

Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner

Curitiba, Paraná, 80060-900, Brazil

Location

Liga Norte Riograndense Contra O Cancer

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

Associação Hospital de Caridade Ijuí

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital Bruno Born

Lajeado, Rio Grande do Sul, 95900-000, Brazil

Location

Universidade Federal do Rio Grande do Sul - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Location

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

Location

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Clínica de Oncologia de Porto Alegre SS Ltda

Rio Grande, Rio Grande do Sul, 90430-090, Brazil

Location

Instituto Joinvilense de Hematologia E Oncologia

Joinville, Santa Catarina, 89201-260, Brazil

Location

Fundação Pio XII Hospital de Câncer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital das Clinicas - UNICAMP

Campinas, São Paulo, 13083-887, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

Fundação do ABC - Faculdade de Medicina do ABC

Santo André, São Paulo, 09060-650, Brazil

Location

Instituto de Pesquisas Clínicas Para Estudos Multicêntricos

Caxias do Sul, 95070-560, Brazil

Location

Instituto Do Câncer Do Ceará ICC

Fortaleza, 60430-230, Brazil

Location

Animi

Lages, 88501-001, Brazil

Location

Instituto Nacional de Câncer

Rio de Janeiro, 20231-050, Brazil

Location

Instituto COI de Pesquisa, Educação e Gestão

Rio de Janeiro, 22793-080, Brazil

Location

Hospital de Base Da Faculdade de Medicina de São José Do Rio Preto

São José do Rio Preto, 15090-000, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, 01323-903, Brazil

Location

Fundação Antônio Prudente - AC Camargo Câncer Center

São Paulo, 01508-010, Brazil

Location

Hospital Santa Marcelina

São Paulo, 08270-120, Brazil

Location

Corporacion de Beneficencia Osorno

Osorno, Los Lagos Region, 5311092, Chile

Location

Clinical Research Chile SpA

Valdivia, Los Ríos Region, 5090000, Chile

Location

Oncovida

Santiago, 7500000, Chile

Location

Clinica Santa Maria

Santiago, 7520349, Chile

Location

Fundación Arturo López Pérez (FALP) - PPDS

Santiago, 7850000, Chile

Location

Centro Investigacion Clinica Del Sur

Temuco, 4810371, Chile

Location

Oncocentro APYS

Viña del Mar, 2520612, Chile

Location

Centro de Investigaciones Clínicas Vina del Mar

Viña del Mar, 2540364, Chile

Location

Health Pharma Professional Research S.A de C.V.

Mexico City, Mexico City, 03810, Mexico

Location

Centro de Investigacion Clinica Chapultepec S.A. de C.V.

Morelia, Michoacán, 58260, Mexico

Location

Axis Heilsa S. De R.L. de C.V.

Monterrey, Nuevo León, 64060, Mexico

Location

Accelerium, S. de R.L. de C.V.

Monterrey, 64000, Mexico

Location

Unidad Médica Onco-Hematológica

Puebla City, CP 72530, Mexico

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Clinica Peruana Americana

Trujillo, La Lobertad, 13000, Peru

Location

Clinica Internacional S.A. - Sede San Borja

Lima, 15036, Peru

Location

ONCOCARE S.A.C. (Clinica Aliada)

Lima, 15036, Peru

Location

Hospital Nacional Cayetano Heredia

Lima, 15102, Peru

Location

Altay Regional Oncology Center

Barnaul, 656049, Russia

Location

Chelyabinsk Regional Clinical Oncology Dispensary

Chelyabinsk, 454087, Russia

Location

LLC Evimed

Chelyabinsk, 454087, Russia

Location

Kursk Regional Oncology Centre

Kursk, 305035, Russia

Location

Central Clinical Hospital With Polyclinic of President Administration of RF

Moscow, 121359, Russia

Location

Federal State Institution Medical Radiology Research Center

Obninsk, 249036, Russia

Location

Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

PMI Euromedservice

Pushkin, 196603, Russia

Location

Hospital Orkli LLC

Saint Petersburg, 194044, Russia

Location

Railway Clinical Hospital JSC RZhD

Saint Petersburg, 195271, Russia

Location

Hospital Orkli LLC

Saint Petersburg, 197136, Russia

Location

State Institution of Healthcare "Volgograd Regional Urology and Nephrology Centre"

Volzhskiy, 404120, Russia

Location

Regional Clinical Oncology Hospital

Yaroslavl, 150040, Russia

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Oncocare Cancer Centre

Singapore, 258500, Singapore

Location

Related Publications (1)

• Tannir NM, Formiga MN, Penkov K, Kislov N, Vasiliev A, Gunnar Skare N, Hong W, Dai S, Tang L, Qureshi A, Zalevsky J, Tagliaferri MA, George D, Agarwal N, Pal S. Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09). J Clin Oncol. 2024 Aug 10;42(23):2800-2811. doi: 10.1200/JCO.23.02082. Epub 2024 Jun 5.

  PMID: 38838287 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

bempegaldesleukin; Sunitinib; Nivolumab; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

StudyInquiry@nektar.com

4154825300

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2018
• First Posted: November 2, 2018
• Study Start: December 18, 2018
• Primary Completion: January 7, 2022
• Study Completion: October 19, 2022
• Last Updated: April 11, 2023
• Results First Posted: April 11, 2023

Record last verified: 2023-03

Locations

SG (2); PE (4); AU (5); RU (13); BR (27); AR (11); ME (5); US (20); CL (8); NZ (1)