A Single-Arm Study of Bempegaldesleukin (NKTR-214) Plus Nivolumab in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer

NCT03785925 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 18-214-10CA045-0122018-003636-79
• Study Type: interventional
• Target: 192
• Locations: 18 countries
• Sites: 70

Brief Summary

The main purpose of this study is to evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients.

Conditions

Urinary Bladder Neoplasm; Neoplasm Metastasis

Keywords

Bladder; Bladder Cancer; CD122; Cisplatin Ineligible; Immuno-oncology; Immunotherapy; Locally Advanced Urothelial Cancer; Metastatic Urothelial Cancer; mUC; Natural Killer Cells; Nivolumab; NKTR-214; Opdivo®; PD-L1; Urothelial Cancer; Urothelial; Metastatic Urothelial Carcinoma; Urothelial Carcinoma; Bempegaldesleukin; BEMPEG; CPI Combination; IL-2

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression

  To evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the ORR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in patients whose tumors have low programmed cell death ligand 1 (PD-L1) expression. ORR was defined as the percentage of patients with confirmed objective response of Complete Response (CR) or Partial Response (PR) on or before the first progressive disease and any subsequent anticancer therapy. 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.

  Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months

Secondary Outcomes (4)

• Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in All Treated Patients

  Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.

• Duration of Response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression

  Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.

• Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression

  Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.

• Duration of Response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression

  Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months.

Study Arms (1)

Combination of bempegaldesleukin (NKTR-214) + nivolumab

EXPERIMENTAL

Participants will receive bempegaldesleukin (NKTR-214) in combination with nivolumab.

Biological: Bempegaldesleukin; Biological: Nivolumab

Interventions

Bempegaldesleukin BIOLOGICAL

Specified dose on specified days

Also known as: NKTR-214, BMS-986321

Combination of bempegaldesleukin (NKTR-214) + nivolumab

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo®, BMS-936658

Combination of bempegaldesleukin (NKTR-214) + nivolumab

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
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Measurable disease per RECIST 1.1 criteria
• Histologically or cytologically documented inoperable, locally advanced or metastatic urothelial cell carcinoma (also termed TCC)
• Fresh biopsy or archival tissue
• No prior systemic chemotherapy or investigational agent for inoperable locally advanced or mUC
• Ineligible for cisplatin

You may not qualify if:

• Patients who have an active, known or suspected autoimmune disease
• Patients must not have received prior IL-2 therapy
• Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patients with hypertension must be on a stable antihypertensive regimen for the 14 days prior to Cycle 1 Day 1

Sponsors & Collaborators

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

Study Sites (70)

San Francisco VA Medical Center - NAVREF - PPDS

San Francisco, California, 94143, United States

Location

Innovative Clinical Research Institute, LLC

Whittier, California, 90603, United States

Location

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Southeastern Regional Medical Center - CTCA - PPDS

Newnan, Georgia, 30265, United States

Location

Investigator Site - Peoria

Peoria, Illinois, 61615, United States

Location

Laura And Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Centro de Investigación Clínica - Clínica Viedma

Viedma, Río Negro Province, R8500ACE, Argentina

Location

Instituto de Oncologia de Rosario

Rosario, Santa Fe Province, S2000DSK, Argentina

Location

CAIPO Centro para la atención integral del paciente oncológico

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Hospital Alemán

Buenos Aires, C1118AAT, Argentina

Location

Instituto Médico Especializado Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Centro Médico Privado CEMAIC

Córdoba, X5000HHW, Argentina

Location

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

Córdoba, X5002AOQ, Argentina

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Tasman Health Care

Southport, Queensland, 4215, Australia

Location

Adelaide Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Monash Health, Monash Medical Centre

Bentleigh East, Victoria, 3165, Australia

Location

St John of God Murdoch Hospital

Nedlands, Western Australia, 6009, Australia

Location

Algemeen Ziekenhuis Klina

Brasschaat, Antwerpen, 2930, Belgium

Location

GasthuisZusters Antwerpen

Wilrijk, Antwerpen, 2610, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Helsingin Yliopistollinen Keskussairaala - PPDS

Helsinki, 00290, Finland

Location

Centre François Baclesse

Caen, Calvados, 14076, France

Location

Hôpital Privé TOULON/HYERES Sainte Marguerite

Hyères, 83400, France

Location

Centre Jean Bernard Clinique Victor Hugo

Le Mans, 72015, France

Location

Hôpital Européen Georges Pompidou

Paris, 75908, France

Location

Edog Ico - Ppds

Saint-Herblain, 44805, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Studienpraxis Urologie

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

Kliniken Nordoberpfalz AG

Weiden, Bavaria, 92637, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Alexandra Hospital

Athens, Attica, 115 28, Greece

Location

Medical Center of Athens

Marousi, Attica, 151 25, Greece

Location

University General Hospital of Larissa

Larissa, 41110, Greece

Location

Euromedica - PPDS

Thessaloniki, 54645, Greece

Location

Shamir Medical Center Assaf Harofeh

Ẕerifin, Central District, 70300, Israel

Location

Rambam Medical Center - PPDS

Haifa, 31096, Israel

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

Sheba Medical Center - PPDS

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center PPDS

Tel Aviv, 52620, Israel

Location

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, Emilia-Romagna, 47014, Italy

Location

Centro Di Riferimento Oncologico

Aviano, Pordenone, 33081, Italy

Location

Istituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

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

Mexico City, Mexico City, 03810, Mexico

Location

Phylasis Clinicas Research S. de R.L. de C.V.

Cuautitlán Izcalli, 54769, Mexico

Location

Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066, Netherlands

Location

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

Regional Clinical Oncology Hospital

Yaroslavl, Yaroslavl Oblast, 150040, 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

Railway Clinical Hospital JSC RZhD

Saint Petersburg, 195271, Russia

Location

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, Catalonia, 08025, Spain

Location

Hospital Universitario Ramon y Cajal

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Ankara University Medical Faculty - PPDS

Ankara, 6100, Turkey (Türkiye)

Location

Izmir Medicalpark Hospital

Izmir, 35530, Turkey (Türkiye)

Location

Inonu University Faculty of Medicine Turgut Ozal Medical Center

Malatya, 44280, Turkey (Türkiye)

Location

Royal Marsden Hospital - Surrey

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Barts Health NHS Trust

London, EC1A 7BE, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasm Metastasis; Carcinoma, Transitional Cell

Interventions

bempegaldesleukin; Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

855-482-8676

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 24, 2018
• Study Start: April 29, 2019
• Primary Completion: February 9, 2022
• Study Completion: June 30, 2022
• Last Updated: March 28, 2023
• Results First Posted: March 28, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); AR (7); RU (5); US (8); TU (3); BE (3); IT (3); NL (1); ME (2); ES (8); CA (1); IL (5); PT (1); GB (3); AU (5); FR (6); GR (4); FI (1)