A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma
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ClinicalTrials.gov Identifier: NCT03635983 |
Recruitment Status :
Active, not recruiting
First Posted : August 17, 2018
Results First Posted : December 19, 2022
Last Update Posted : May 10, 2023
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Condition or disease | Intervention/treatment | Phase |
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Melanoma | Biological: NKTR-214 Biological: Nivolumab | Phase 3 |
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 |

Arm | Intervention/treatment |
---|---|
Experimental: Combination
NKTR-214 + Nivolumab
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Biological: NKTR-214
Specified dose on specified days
Other Names:
Biological: Nivolumab Specified dose on specified days
Other Names:
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Experimental: Monotherapy
Nivolumab
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Biological: Nivolumab
Specified dose on specified days
Other Names:
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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

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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 |
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

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

Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: | May 10, 2023 |
Last Verified: | May 2023 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
NKTR-214 Nivolumab Immunotherapy bempegaldesleukin (BEMPEG: NKTR-214) |
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 |