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

Phase 2

Completed

Conditions: Urinary Bladder Neoplasm
Neoplasm Metastasis

Interventions: Biological: Bempegaldesleukin
Biological: Nivolumab

Registration Number: NCT03785925

Lead Sponsor: Nektar Therapeutics

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 192

Inclusion Criteria

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

Key

Exclusion Criteria

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

Additional protocol-defined inclusion/exclusion criteria applied

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of bempegaldesleukin (NKTR-214) + nivolumab	Nivolumab	Participants will receive bempegaldesleukin (NKTR-214) in combination with nivolumab.
Combination of bempegaldesleukin (NKTR-214) + nivolumab	Bempegaldesleukin	Participants will receive bempegaldesleukin (NKTR-214) in combination with nivolumab.

Primary Outcome Measures

Name	Time	Method
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	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	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.

Secondary Outcome Measures

Name	Time	Method
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.	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) by Investigator Assessment in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (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.
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.	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 all treated patients. 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.
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.	To evaluate the effect of NKTR 214 in combination with nivolumab by assessing DOR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in all treated patients and patients whose tumors have low PD-L1 expression. DOR is defined for patients who have a confirmed Complete Response (CR) or Partial Response (PR) as the date from first documented CR or PR per RECIST 1.1 to the date of documentation of disease progression as assessed by BICR or death due to any cause, whichever is earlier. Patients who do not have disease progression or die will be censored on the date of their last evaluable tumor assessment.
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.	To evaluate the effect of NKTR 214 in combination with nivolumab by assessing DOR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Investigator Assessment in all treated patients and patients whose tumors have low PD-L1 expression. DOR is defined for patients who have a confirmed Complete Response (CR) or Partial Response (PR) as the date from first documented CR or PR per RECIST 1.1 to the date of documentation of disease progression as assessed by BICR or death due to any cause, whichever is earlier. Patients who do not have disease progression or die will be censored on the date of their last evaluable tumor assessment.

Trial Locations

Locations (70): Hospital Universitario Ramon y Cajal
🇪🇸
Pozuelo De Alarcón, Madrid, Spain
Centre François Baclesse
🇫🇷
Caen, Calvados, France
Medical Center of Athens
🇬🇷
Maroúsi, Attiki, Greece
Sheba Medical Center - PPDS
🇮🇱
Ramat Gan, Israel
Studienpraxis Urologie
🇩🇪
Nürtingen, Baden-Württemberg, Germany
Kliniken Nordoberpfalz AG
🇩🇪
Weiden, Bavaria, Germany
Instituto de Oncologia de Rosario
🇦🇷
Rosario, Santa Fe, Argentina
Centro de Investigación Clínica - Clínica Viedma
🇦🇷
Viedma, Rio Negro, Argentina
AZ Groeninge
🇧🇪
Kortrijk, Belgium
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Centro Médico Privado CEMAIC
🇦🇷
Córdoba, Argentina
Algemeen Ziekenhuis Klina
🇧🇪
Brasschaat, Antwerpen, Belgium
GasthuisZusters Antwerpen
🇧🇪
Wilrijk, Antwerpen, Belgium
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱
Amsterdam, Netherlands
Sanatorio Privado Duarte Quirós, de Clínica Colombo S.A.
🇦🇷
Córdoba, Argentina
Helsingin Yliopistollinen Keskussairaala - PPDS
🇫🇮
Helsinki, Finland
Alexandra Hospital
🇬🇷
Athens, Attiki, Greece
Meir Medical Center
🇮🇱
Kefar Saba, Israel
Health Pharma Professional Research S.A de C.V.
🇲🇽
Ciudad de mexico, Distrito Federal, Mexico
Phylasis Clinicas Research S. de R.L. de C.V.
🇲🇽
Cuautitlán Izcalli, Mexico
Centro Hospitalar E Universitário de Coimbra EPE
🇵🇹
Coimbra, Portugal
Federal State Institution Medical Radiology Research Center
🇷🇺
Obninsk, Russian Federation
Hospital General Universitario de Elche
🇪🇸
Elche, Alicante, Spain
CAIPO Centro para la atención integral del paciente oncológico
🇦🇷
San Miguel De Tucumán, Tucumán, Argentina
University Health Network
🇨🇦
Toronto, Ontario, Canada
Hospital Alemán
🇦🇷
Buenos Aires, Argentina
University General Hospital of Larissa
🇬🇷
Larissa, Greece
Shamir Medical Center Assaf Harofeh
🇮🇱
Zerifin, HaMerkaz, Israel
Tel Aviv Sourasky Medical Center PPDS
🇮🇱
Tel Aviv, Israel
PMI Euromedservice
🇷🇺
Pushkin, Russian Federation
Royal Marsden Hospital - Surrey
🇬🇧
Sutton, Surrey, United Kingdom
Innovative Clinical Research Institute, LLC
🇺🇸
Whittier, California, United States
San Francisco VA Medical Center - NAVREF - PPDS
🇺🇸
San Francisco, California, United States
Winship Cancer Institute, Emory University
🇺🇸
Atlanta, Georgia, United States
Southeastern Regional Medical Center - CTCA - PPDS
🇺🇸
Newnan, Georgia, United States
Investigator Site - Peoria
🇺🇸
Peoria, Illinois, United States
Laura And Isaac Perlmutter Cancer Center
🇺🇸
New York, New York, United States
Instituto Médico Especializado Alexander Fleming
🇦🇷
Buenos Aires, Argentina
St Vincent's Hospital Sydney
🇦🇺
Darlinghurst, New South Wales, Australia
Tasman Health Care
🇦🇺
Southport, Queensland, Australia
Adelaide Cancer Centre
🇦🇺
Kurralta Park, South Australia, Australia
Monash Health, Monash Medical Centre
🇦🇺
Bentleigh East, Victoria, Australia
St John of God Murdoch Hospital
🇦🇺
Nedlands, Western Australia, Australia
Hôpital Privé TOULON/HYERES Sainte Marguerite
🇫🇷
Hyères, France
Centre Jean Bernard Clinique Victor Hugo
🇫🇷
Le Mans, France
Institut Gustave Roussy
🇫🇷
Villejuif, France
Hôpital Européen Georges Pompidou
🇫🇷
Paris, France
Edog Ico - Ppds
🇫🇷
Saint-Herblain, France
Charité - Universitätsmedizin Berlin
🇩🇪
Berlin, Germany
Universitätsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪
Dresden, Germany
Euromedica - PPDS
🇬🇷
Thessaloníki, Greece
Rambam Medical Center - PPDS
🇮🇱
Haifa, Israel
Centro Di Riferimento Oncologico
🇮🇹
Aviano, Pordenone, Italy
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
🇮🇹
Meldola, Emilia-Romagna, Italy
Istituto Nazionale Dei Tumori
🇮🇹
Milano, Italy
Regional Clinical Oncology Hospital
🇷🇺
Yaroslavl, Yaroslavskaya Oblast, Russian Federation
Clinical Oncology Dispensary
🇷🇺
Omsk, Russian Federation
Railway Clinical Hospital JSC RZhD
🇷🇺
Saint Petersburg, Russian Federation
Hospital de La Santa Creu i Sant Pau
🇪🇸
Barcelona, Catalonia, Spain
Hospital del Mar
🇪🇸
Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Hospital Universitario Virgen del Rocio - PPDS
🇪🇸
Sevilla, Spain
Ankara University Medical Faculty - PPDS
🇹🇷
Ankara, Turkey
Hospital Universitario HM Sanchinarro - CIOCC
🇪🇸
Madrid, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸
Valencia, Spain
Izmir Medicalpark Hospital
🇹🇷
İzmir, Turkey
Inonu University Faculty of Medicine Turgut Ozal Medical Center
🇹🇷
Malatya, Turkey
Barts Health NHS Trust
🇬🇧
London, United Kingdom
Leicester Royal Infirmary
🇬🇧
Leicester, United Kingdom
Rocky Mountain Cancer Centers
🇺🇸
Aurora, Colorado, United States