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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03635983
Recruitment Status : Active, not recruiting
First Posted : August 17, 2018
Results First Posted : December 19, 2022
Last Update Posted : March 15, 2023
Sponsor:
Collaborator:
Nektar Therapeutics
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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Brief 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

Condition or disease Intervention/treatment Phase
Melanoma Biological: NKTR-214 Biological: Nivolumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 783 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 21, 2018
Actual Primary Completion Date : November 19, 2021
Estimated Study Completion Date : February 26, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Combination
NKTR-214 + Nivolumab
 Biological: NKTR-214
Specified dose on specified days
Other Names:
  • Bempegaldesleukin
  • BMS-986321

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-936558
Experimental: Monotherapy
Nivolumab
 Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-936558


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  2. Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) [ Time Frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months) ]
    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.

  3. Overall Survival (OS) [ Time Frame: From date of randomization to date of death (Up to 37 months) ]
    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.


Secondary Outcome Measures :
  1. Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR) [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  2. Duration of Response (DoR) Per Blinded Independent Central Review (BICR) [ Time Frame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months) ]
    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.

  3. Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR) [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  4. Objective Response Rate (ORR) Per Investigator [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  5. Progression-free Survival (PFS) Per Investigator [ Time Frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months) ]
    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.

  6. Clinical Benefit Rate (CBR) Per Investigator [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  7. Duration of Response (DoR) Per Investigator [ Time Frame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months) ]
    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.

  8. Time to Objective Response (TTR) Per Investigator [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  9. Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status [ Time Frame: From date of randomization to disease progression (Up to 37 months) ]
    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.

  10. Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status [ Time Frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months) ]
    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.

  11. Overall Survival (OS) by Baseline PD-L1 Status [ Time Frame: From date of randomization to date of death (Up to 37 months) ]
    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.

  12. Number of Participants With Adverse Events (AEs) [ Time Frame: From first dose to 30 days post last dose (Average of 8 months and a maximum up to 35 months) ]
    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.

  13. Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline [ Time Frame: From first dose to 100 days post last dose (Average of 10 months and a maximum up to 37 months) ]

    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



Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03635983


Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Nektar Therapeutics
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol and Statistical Analysis Plan  [PDF] May 19, 2022

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03635983    
Other Study ID Numbers: CA045-001
2018-001423-40 ( EudraCT Number )
17-214-08 ( Other Identifier: Nektar Therapeutics )
First Posted: August 17, 2018    Key Record Dates
Results First Posted: December 19, 2022
Last Update Posted: March 15, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bristol-Myers Squibb:
NKTR-214
Nivolumab
Immunotherapy
bempegaldesleukin (BEMPEG: NKTR-214)
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
 Nevi and Melanomas
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action