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

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with at least 6 months of follow-up at the time point of the final ORR analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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.

Time frame: From date of randomization to date of death (Up to 37 months)

Population: All randomized participants

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.

Time frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)

Population: All randomized participants

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with at least 6 months of follow-up at the time point of the final ORR analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with at least 6 months of follow-up at the time point of the final ORR analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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 frame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)

Population: All randomized participants with partial or complete response and at least 6 months of follow-up at the time point of the final objective response rate analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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 frame: From date of randomization to disease progression, or death, whichever is earlier (Up to 37 months)

Population: All randomized participants with partial or complete response and at least 6 months of follow-up at the time point of the final objective response rate analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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.

Time frame: From first dose to 30 days post last dose (Average of 11 months and a maximum up to 26 months)

Population: All treated participants

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

Time frame: From first dose to 100 days post last dose (Average of 13 months and a maximum up to 28 months)

Population: All treated participants with laboratory baseline measures

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with PD-L1 data available at baseline and at least 6 months of follow-up at the time point of the final objective response rate analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with at least 6 months of follow-up at the time point of the final ORR analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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.

Time frame: From date of randomization to date of death (Up to 37 months)

Population: All randomized participants with PD-L1 data available at baseline

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.

Time frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)

Population: All randomized participants with PD-L1 data available at baseline

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.

Time frame: From date of randomization to disease progression, or death, whichever comes first (Up to 37 months)

Population: All randomized participants

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with partial or complete response and at least 6 months of follow-up at the time point of the final objective response rate analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date.

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.

Time frame: From date of randomization to disease progression (Up to 37 months)

Population: All randomized participants with partial or complete response and at least 6 months of follow-up at the time point of the final objective response rate analysis. A follow-up time is defined as the time between randomization date and clinical data cut-off date