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

Neoplasm Metastasis Clinical Trial

— PIVOT-10  

Official title:

A Phase 2, Single-Arm Study of Bempegaldesleukin (NKTR-214) in Combination With Nivolumab in Cisplatin Ineligible, Locally Advanced or Metastatic Urothelial Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03785925
• Other study ID #: 18-214-10
• Secondary ID: CA045-0122018-00
• Status: Completed
• Phase: Phase 2
• Start date: April 29, 2019
• Est. completion date: June 30, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: June 30, 2022
• Est. primary completion date: February 9, 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

• 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

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Neoplasms
• Urinary Bladder Neoplasm
• Urinary Bladder Neoplasms

Intervention

Biological:
• Bempegaldesleukin
Specified dose on specified days
• Nivolumab
Specified dose on specified days

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Nektar Therapeutics	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Finland,  France,  Germany,  Greece,  Israel,  Italy,  Mexico,  Netherlands,  Portugal,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in All Treated Patients	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.	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	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	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.	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	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	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.	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	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	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.	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.