A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma

Melanoma Clinical Trial

Official title:

A Phase 3, Randomized, Open-label Study of NKTR-214 Combined With Nivolumab Versus Nivolumab in Participants With Previously Untreated Unresectable or Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03635983
• Other study ID #: CA045-001
• Secondary ID: 2018-001423-4017
• Status: Completed
• Phase: Phase 3
• Start date: September 21, 2018
• Est. completion date: September 6, 2023

Study information

• Verified date: October 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to test the effectiveness (how well the drug works), safety, and tolerability of the investigational drug called NKTR-214, when combined with nivolumab versus nivolumab given alone in participants with previously untreated melanoma skin cancer that is either unable to be surgically removed or has spread

Recruitment information / eligibility

• Status: Completed
• Enrollment: 783
• Est. completion date: September 6, 2023
• Est. primary completion date: November 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of =1 (adults 18 years or older)/Lansky Performance Score = 80% (minors ages 12-17 only)
• Histologically confirmed stage III (unresectable) or stage IV melanoma
• Treatment-naive participants (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma) with the exception of prior adjuvant and/or neoadjuvant treatment for melanoma with approved agents

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases
• Uveal melanoma
• Participants with an active, known or suspected autoimmune disease Other protocol defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• NKTR-214
Specified dose on specified days
• Nivolumab
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0107	Buenos Aires	Ciudad Autónoma De Buenos Aires
Argentina	Local Institution - 0183	Buenos Aires	Distrito Federal
Argentina	Local Institution - 0108	Caba
Argentina	Local Institution - 0109	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 0157	Cordoba
Australia	Local Institution - 0058	Cairns	Queensland
Australia	Local Institution - 0146	Coffs Harbour	New South Wales
Australia	Local Institution - 0172	Elizabeth Vale	South Australia
Australia	Local Institution	Greenslopes	Queensland
Australia	Local Institution - 0054	Melbourne	Victoria
Australia	Local Institution - 0143	Melbourne	Victoria
Australia	Local Institution - 0057	Nedlands	Western Australia
Australia	Local Institution - 0097	Nedlands	Western Australia
Australia	Local Institution - 0053	North Sydney	New South Wales
Australia	Local Institution - 0056	Woolloongabba	Queensland
Austria	Local Institution - 0034	Graz
Austria	Local Institution - 0035	Salzburg
Austria	Local Institution - 0033	Wien
Belgium	Local Institution - 0083	Bruxelles
Belgium	Local Institution - 0084	Hasselt
Belgium	Local Institution - 0085	Leuven
Brazil	Local Institution - 0126	Barretos	Sao Paulo
Brazil	Local Institution - 0125	Belo Horizonte	Minas Gerais
Brazil	Local Institution - 0168	Fortaleza	Ceara
Brazil	Local Institution - 0124	Ijui	RIO Grande DO SUL
Brazil	Local Institution - 0171	Itajai	Santa Catarina
Brazil	Local Institution - 0127	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0182	Rio De Janeiro
Brazil	Local Institution - 0169	Sao Paulo
Canada	Local Institution - 0068	Abbotsford	British Columbia
Canada	Local Institution - 0121	Edmonton
Canada	Local Institution - 0066	Hamilton	Ontario
Canada	Local Institution - 0067	Kitchener	Ontario
Canada	Local Institution	Quebec
Canada	Local Institution - 0139	St. John's	Newfoundland and Labrador
Canada	Local Institution - 0041	Toronto	Ontario
Chile	Local Institution - 0174	Recoleta	Metropolitana
Chile	Local Institution - 0173	Santiago	Metropolitana
Czechia	Local Institution - 0094	Brno
Czechia	Local Institution - 0093	Hradec Kralove
Czechia	Local Institution - 0091	Praha 10
Czechia	Local Institution - 0092	Praha 2
Finland	Local Institution - 0167	KYS
Finland	Local Institution - 0166	Tampere	Oulun Lääni
Finland	Local Institution - 0165	Turku
France	Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre	Bordeaux
France	Hopital Claude Huriez	Lille
France	Hopital Saint Eloi	Montpellier Cedex 05
France	Hotel Dieu - Chu De Nantes	Nantes Cedex 1
France	Chu De Nice Hopital De Cimiez	Nice
France	Hopital Saint Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU Charles Nicolle	Rouen
France	Hopital Nord - CHU de Saint-Etienne	Saint Priest en Jarez
France	Institut Claudius Regaud	Toulouse Cedex 9
France	Institute Gustave Roussy	Villejuif
Germany	Local Institution - 0031	Buxtehude
Germany	Local Institution - 0029	Dresden
Germany	Local Institution - 0192	Erfurt
Germany	Local Institution - 0026	Essen
Germany	Local Institution - 0030	Goettingen
Germany	Local Institution - 0023	Hamburg
Germany	Local Institution - 0024	Hannover
Germany	Local Institution - 0020	Heidelberg
Germany	Local Institution - 0028	Kiel
Germany	Local Institution - 0022	Leipzig
Germany	Local Institution - 0021	Muenchen
Germany	Local Institution - 0027	Münster
Germany	Local Institution - 0060	Regensburg
Germany	Local Institution - 0025	Tuebingen
Germany	Local Institution - 0032	Wuerzburg
Greece	Local Institution - 0038	Athens
Greece	Local Institution - 0039	Neo Faliro
Greece	Local Institution - 0040	Thessaloniki
Ireland	Local Institution - 0128	Dublin
Ireland	Local Institution - 0130	Dublin
Ireland	Local Institution - 0129	Dublin 7	Dublin
Ireland	Local Institution - 0136	Wilton	Cork
Israel	Local Institution - 0098	Beer Sheva
Israel	Local Institution - 0088	Jerusalem
Israel	Local Institution - 0089	Ramat-gan
Italy	IRCCS Giovanni Paolo II Istituto Oncologico	Bari
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	IRST Meldola	Meldola (fc)
Italy	Istituto Europeo di Oncologia IRCCS	Milan	Lombardia
Italy	IRCCS Istituto Nazionale Tumori Milano	Milano
Italy	Instituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Istituto Oncologico Veneto IOV	Padova
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino	Piemonte
Italy	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Torino
Mexico	Local Institution - 0178	Cancún	Quintana Roo
Mexico	Local Institution - 0175	Ciudad de Mexico	Distrito Federal
Mexico	Local Institution - 0177	Monterrey	Nuevo LEON
Mexico	Local Institution - 0180	Monterrey	Nuevo LEON
Mexico	Local Institution - 0179	Puebla
Mexico	Local Institution - 0181	San Luis Potosi
Mexico	Local Institution - 0176	Zapopan	Jalisco
Netherlands	Local Institution - 0101	Amsterdam
Netherlands	Local Institution - 0102	Amsterdam
Netherlands	Local Institution - 0099	Leiden
Netherlands	Local Institution - 0100	Nijmegen
Netherlands	Local Institution - 0147	Untrecht
New Zealand	Local Institution - 0159	Auckland
New Zealand	Local Institution - 0063	Christchurch
New Zealand	Local Institution - 0062	Wellington
Poland	Local Institution - 0152	Bydgoszcz
Poland	Local Institution - 0090	Warszawa
Portugal	Local Institution - 0134	Lisboa
Portugal	Local Institution - 0133	Porto
Romania	Local Institution - 0162	Bucharest
Romania	Local Institution - 0070	Cluj-Napoca
Romania	Local Institution - 0071	Craiova
Romania	Local Institution - 0120	Floresti
Russian Federation	Local Institution - 0149	Krasnoyarsk
Russian Federation	Local Institution - 0086	Moscow
Russian Federation	Local Institution - 0111	Moscow
Russian Federation	Local Institution - 0148	Moscow
Spain	Local Institution - 0115	Barcelona
Spain	Local Institution - 0116	Barcelona
Spain	Local Institution - 0123	Cordoba
Spain	Local Institution - 0190	Doniostia - San Sebastian
Spain	Local Institution	Donostia
Spain	Local Institution - 0118	Jaén
Spain	Local Institution - 0114	Madrid
Spain	Local Institution - 0119	Santiago Compostela
Spain	Local Institution - 0117	Valencia
Sweden	Local Institution - 0163	Gothenburg
Sweden	Local Institution - 0164	Lund
Switzerland	Local Institution - 0104	Bern
Switzerland	Local Institution - 0105	Lausanne
Switzerland	Local Institution - 0036	Zuerich
United Kingdom	Local Institution - 0078	Belfast
United Kingdom	Local Institution - 0076	Cambridge
United Kingdom	Local Institution - 0079	Cottingham
United Kingdom	Local Institution	Edinburgh	Midlothian
United Kingdom	Local Institution - 0137	Liverpool
United Kingdom	Local Institution - 0074	London
United Kingdom	Local Institution - 0077	London
United Kingdom	Local Institution - 0075	Manchester
United Kingdom	Local Institution - 0132	Southampton	Hampshire
United Kingdom	Local Institution - 0131	Sutton.	Surrey
United Kingdom	Local Institution - 0142	Tauton
United States	Local Institution - 0188	Ann Arbor	Michigan
United States	Local Institution - 0012	Atlanta	Georgia
United States	Local Institution - 0051	Aurora	Colorado
United States	Local Institution - 0018	Boston	Massachusetts
United States	Local Institution - 0037	Cleveland	Ohio
United States	St. Luke's Hospital & Health Network	Easton	Pennsylvania
United States	Local Institution - 0064	Fairfax	Virginia
United States	Local Institution - 0186	Fridley	Minnesota
United States	Local Institution - 0016	Hackensack	New Jersey
United States	Local Institution - 0001	Houston	Texas
United States	Local Institution - 0014	La Jolla	California
United States	Local Institution - 0019	Louisville	Kentucky
United States	Local Institution - 0153	Miami	Florida
United States	Local Institution - 0017	Miami Beach	Florida
United States	Local Institution - 0185	New Brunswick	New Jersey
United States	Local Institution - 0065	New Haven	Connecticut
United States	Local Institution - 0141	New York	New York
United States	Local Institution - 0015	Philadelphia	Pennsylvania
United States	Local Institution - 0011	Portland	Oregon
United States	Local Institution - 0013	Portland	Oregon
United States	Local Institution - 0135	Saint Louis	Missouri
United States	Local Institution - 0122	Stanford	California
United States	Local Institution - 0112	Tampa	Florida
United States	Local Institution - 0187	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  Finland,  France,  Germany,  Greece,  Ireland,  Israel,  Italy,  Mexico,  Netherlands,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)	ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) using RECIST v 1.1 per blinded independent central review (BICR) assessment. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression (Up to 37 months)
Primary	Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR)	PFS is defined as the time between the date of randomization and the first date of documented tumor progression using RECIST v 1.1 per blinded independent central review (BICR), or death due to any cause, whichever comes first. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm.	From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Primary	Overall Survival (OS)	OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who do not have a date of death will be censored on the last date for which a participant was known to be alive.	From date of randomization to date of death (Up to 37 months)
Secondary	Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)	CBR, or equivalently the disease control rate (DCR) is defined as the percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review (BICR) using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.	From date of randomization to disease progression (Up to 37 months)
Secondary	Duration of Response (DoR) Per Blinded Independent Central Review (BICR)	DOR is defined for participants who have a confirmed complete response (CR) or partial results (PR) as the date from first documented CR or PR using RECIST v 1.1 to the date of the documentation of disease progression per blinded independent central review (BICR) assessment or death due to any cause, whichever is earlier. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
Secondary	Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)	Time to response (TTR) is defined for participants who had a confirmed complete response (CR) or partial response (PR) as the time from the date of randomization to date of first documented CR or PR per blinded independent central review (BICR) assessment using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression (Up to 37 months)
Secondary	Objective Response Rate (ORR) Per Investigator	ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) using RECIST v 1.1 per investigator assessment. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression (Up to 37 months)
Secondary	Progression-free Survival (PFS) Per Investigator	PFS is defined as the time between the date of randomization and the first date of documented tumor progression using RECIST v 1.1 per investigator, or death due to any cause, whichever comes first. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm.	From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Secondary	Clinical Benefit Rate (CBR) Per Investigator	CBR, or equivalently the disease control rate (DCR) is defined as the percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as assessed by investigator using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	From date of randomization to disease progression (Up to 37 months)
Secondary	Duration of Response (DoR) Per Investigator	DOR is defined for participants who have a confirmed complete response (CR) or partial results (PR) as the date from first documented CR or PR using RECIST v 1.1 to the date of the documentation of disease progression per investigator assessment or death due to any cause, whichever is earlier. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)
Secondary	Time to Objective Response (TTR) Per Investigator	Time to response (TTR) is defined for participants who had a confirmed complete response (CR) or partial response (PR) as the time from the date of randomization to date of first documented CR or PR per investigator assessment using RECIST v 1.1. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression (Up to 37 months)
Secondary	Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status	ORR by baseline PD-L1 tumor cells expression (PD-L1 negative: <1%) vs. (PD-L1 positive: >=1%). ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) using RECIST v 1.1 per blinded independent central review (BICR) assessment. CR=Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions.	From date of randomization to disease progression (Up to 37 months)
Secondary	Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status	PFS by baseline PD-L1 tumor cells expression (PD-L1 negative: <1%) vs. (PD-L1 positive: >=1%). PFS is defined as the time between the date of randomization and the first date of documented tumor progression using RECIST v 1.1 per blinded independent central review (BICR), or death due to any cause, whichever comes first. Progressive disease (PD)=At least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm.	From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)
Secondary	Overall Survival (OS) by Baseline PD-L1 Status	OS by baseline PD-L1 tumor cells expression (PD-L1 negative: <1%) vs. (PD-L1 positive: >=1%). OS is defined as the time between the date of randomization and the date of death due to any cause. Participants who do not have a date of death will be censored on the last date for which a participant was known to be alive.	From date of randomization to date of death (Up to 37 months)
Secondary	Number of Participants With Adverse Events (AEs)	Number of participants with any grade adverse events (AEs) including treatment-related AEs, AEs leading to discontinuation of any drug, serious adverse events (SAEs), treatment-related SAEs, and deaths from first dose to 30 days post last dose. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.	From first dose to 30 days post last dose (Average of 8 months and a maximum up to 35 months)
Secondary	Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline	Number of participants with on-treatment laboratory parameters that worsened relative to baseline. Parameters include hematology, chemistry, liver function, and renal function using worst grade (grade 1-4 and grade 3-4) per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) v5 criteria.; Grade 1=Mild event Grade 2=Moderate event Grade 3=Severe event Grade 4=Life threatening event	From first dose to 100 days post last dose (Average of 10 months and a maximum up to 37 months)

External Links

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