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

• ClinicalTrials.gov Identifier: NCT03635983
• Recruitment Status: Completed
• First Posted: August 17, 2018
• Results First Posted: December 19, 2022
• Last Update Posted: October 18, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Nektar Therapeutics
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma
• Interventions: Biological: NKTR-214; Biological: Nivolumab
• Enrollment: 783

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Period Title: Pre-Treatment Period
Started [1]	391	392
Completed [2]	387	382
Not Completed	4	10
Reason Not Completed
Not yet treated at the time of database lock	1	0
Withdrawal by Subject	0	7
Participant no longer meets study criteria	1	0
Other reasons	1	2
Disease Progression	0	1
Adverse Event unrelated to Study drug	1	0
[1] Started=randomized; [2] Completed=treated
Period Title: Treatment Period
Started [1]	387	382
Completed [2]	135	135
Not Completed	252	247
Reason Not Completed
Completed treatment period	13	20
Participant request to discontinue Study treatment	5	5
Withdrawal by Subject	2	4
Death	3	4
Poor/Non-compliance	1	0
Participant no longer meets Study criteria	0	2
Other reasons	5	2
Disease progression	184	168
Study drug toxicity	26	29
Adverse event unrelated to Study drug	10	11
Maximum clinical benefit	3	2
[1] Started=treated; [2] Completed=on-going treatment

Baseline Characteristics

Arm/Group Title		Bempegaldesleukin + Nivolumab	Nivolumab	Total
Arm/Group Description		Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks	Total of all reporting groups
Overall Number of Baseline Participants		391	392	783
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	391 participants	392 participants	783 participants
		61.3 (13.2)	60.4 (13.5)	60.8 (13.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	391 participants	392 participants	783 participants
	Female	162 41.4%	163 41.6%	325 41.5%
	Male	229 58.6%	229 58.4%	458 58.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	391 participants	392 participants	783 participants
	Hispanic or Latino	81 20.7%	73 18.6%	154 19.7%
	Not Hispanic or Latino	165 42.2%	153 39.0%	318 40.6%
	Unknown or Not Reported	145 37.1%	166 42.3%	311 39.7%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	391 participants	392 participants	783 participants
White		379	379	758
Black or African American		2	4	6
Asian		1	0	1
American Indian or Alaska Native		5	2	7
Other		4	7	11

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	271	272
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	27.7; (22.4 to 33.4)	36.0; (30.3 to 42.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab over Nivolumab
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0311
	Comments	[Not Specified]
	Method	Stratified Cochran-Mantel-Haenszel
	Comments	two-sided
Method of Estimation	Estimation Parameter	Estimate of Odds Ratio (OR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.96
	Estimation Comments	Strata adjusted odds ratio (NKTR-214 + Nivolumab over Nivolumab) using Mantel-Haenszel method.

2. Primary Outcome

Title	Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR)
Description	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)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	391	392
Median (95% Confidence Interval); Unit of Measure: Months
	4.17; (3.52 to 5.55)	4.99; (4.14 to 7.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3988
	Comments	Log-rank stratified 2-sided. Boundary for statistical significance p-value < 0.03
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	95%; 0.89 to 1.33
	Estimation Comments	Stratified Cox proportional hazard model. Hazard Ratio is NKTR-214 + Nivolumab over Nivolumab

3. Primary Outcome

Title	Overall Survival (OS)
Description	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)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	391	392
Median (95% Confidence Interval); Unit of Measure: Months
	29.67 [1]; (22.14 to NA)	28.88 [1]; (21.32 to NA)

[1]

insufficient number of participants with events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Bempegaldesleukin+Nivolumab over Nivolumab
Statistical Test of Hypothesis	P-Value	0.6361
	Comments	[Not Specified]
	Method	Log Rank
	Comments	2-sided p-value. Boundary for statistical significance p-value < 0.00071
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.22
	Estimation Comments	Stratified Cox proportional hazard model. Hazard Ratio is NKTR-214 + Nivolumab over Nivolumab.

4. Secondary Outcome

Title	Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	271	272
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	56.1; (50.0 to 62.1)	58.5; (52.4 to 64.4)

5. Secondary Outcome

Title	Duration of Response (DoR) Per Blinded Independent Central Review (BICR)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	75	98
Median (95% Confidence Interval); Unit of Measure: Months
	29.67 [1]; (18.89 to NA)	NA [1]; (26.74 to NA)

[1]

insufficient number of participants with events

6. Secondary Outcome

Title	Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	75	98
Median (Full Range); Unit of Measure: Months
	2.17; (1.0 to 15.3)	2.20; (1.2 to 15.5)

7. Secondary Outcome

Title	Objective Response Rate (ORR) Per Investigator
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	271	272
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	29.2; (23.8 to 35.0)	36.4; (30.7 to 42.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab over Nivolumab
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0626
	Comments	[Not Specified]
	Method	Stratified Cochran-Mantel-Haenszel
	Comments	two-sided
Method of Estimation	Estimation Parameter	Estimate of Odds Ratio (OR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.02
	Estimation Comments	Strata adjusted odds ratio (NKTR-214 + Nivolumab over Nivolumab) using Mantel-Haenszel method.

8. Secondary Outcome

Title	Progression-free Survival (PFS) Per Investigator
Description	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)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	391	392
Median (95% Confidence Interval); Unit of Measure: Months
	4.27; (4.04 to 6.14)	6.21; (4.60 to 10.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3713
	Comments	Log-rank stratified 2-sided. Boundary for statistical significance p-value < 0.03
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	95%; 0.90 to 1.33
	Estimation Comments	Stratified Cox proportional hazard model. Hazard Ratio is NKTR-214 + Nivolumab over Nivolumab

9. Secondary Outcome

Title	Clinical Benefit Rate (CBR) Per Investigator
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	271	272
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	60.5; (54.4 to 66.4)	61.8; (55.7 to 67.6)

10. Secondary Outcome

Title	Duration of Response (DoR) Per Investigator
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	79	99
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (17.31 to NA)	NA [1]; (21.68 to NA)

[1]

insufficient number of participants with events

11. Secondary Outcome

Title	Time to Objective Response (TTR) Per Investigator
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	79	99
Median (Full Range); Unit of Measure: Months
	2.14; (1.6 to 18.3)	2.14; (1.8 to 12.2)

12. Secondary Outcome

Title	Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:		Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed		242	248
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Participants with baseline PD-L1 expression <1%	Number Analyzed	102 participants	107 participants
		17.6; (10.8 to 26.4)	25.2; (17.3 to 34.6)
Participants with baseline PD-L1 expression >=1%	Number Analyzed	140 participants	141 participants
		36.4; (28.5 to 45.0)	47.5; (39.1 to 56.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab vs. Nivolumab (PD-L1 Negative: <1%)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.63
	Confidence Interval	95%; 0.32 to 1.24
	Estimation Comments	Logistic regression model with treatment, PD-L1 Status and treatment by PD-L1 Status interaction. Responders includes CR+PR

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab vs. Nivolumab (PD-L1 Positive: >=1%)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9939
	Comments	[Not Specified]
	Method	Stratified Cochran-Mantel-Haenszel
	Comments	Interaction P-value
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.02
	Estimation Comments	Logistic regression model with treatment, PD-L1 Status and treatment by PD-L1 Status interaction. Responders includes CR+PR

13. Secondary Outcome

Title	Progression-free Survival (PFS) Per Blinded Independent Central Review (BICR) by Baseline PD-L1 Status
Description	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)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 data available at baseline

Arm/Group Title		Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:		Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed		349	357
Median (95% Confidence Interval); Unit of Measure: Months
Participants with baseline PD-L1 expression <1%	Number Analyzed	156 participants	163 participants
		3.25; (2.20 to 4.24)	2.30; (2.17 to 4.17)
Participants with baseline PD-L1 expression >=1%	Number Analyzed	193 participants	194 participants
		6.24; (4.47 to 10.45)	10.51; (6.05 to 28.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab vs. Nivo (PD-L1 negative: <1%)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.43
	Estimation Comments	Unstratified Hazard Ratio

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab vs. Nivo (PD-L1 positive: >=1%)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	95%; 0.83 to 1.51
	Estimation Comments	Unstratified Hazard Ratio

14. Secondary Outcome

Title	Overall Survival (OS) by Baseline PD-L1 Status
Description	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)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 data available at baseline

Arm/Group Title		Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:		Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed		349	357
Median (95% Confidence Interval); Unit of Measure: Months
Participants with baseline PD-L1 expression <1%	Number Analyzed	156 participants	163 participants
		21.16; (15.51 to 26.68)	21.13 [1]; (16.62 to NA)
Participants with baseline PD-L1 expression >=1%	Number Analyzed	193 participants	194 participants
		NA [1]; (29.67 to NA)	NA [1]; (28.88 to NA)

[1]

insufficient number of participants with events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab vs. Nivo (PD-L1 negative: <1%)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.40
	Estimation Comments	Unstratified Hazard Ratio

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bempegaldesleukin + Nivolumab, Nivolumab
	Comments	Bempegaldesleukin+Nivolumab vs. Nivo (PD-L1 positive: >=1%)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	95%; 0.58 to 1.33
	Estimation Comments	Unstratified Hazard Ratio

15. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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 8 months and a maximum up to 35 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed	387	382
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	369 95.3%	351 91.9%
Drug-related AEs	343 88.6%	264 69.1%
SAEs	123 31.8%	112 29.3%
Drug-related SAEs	54 14.0%	26 6.8%
AEs leading to discontinuation of any Drug	58 15.0%	45 11.8%
Deaths	19 4.9%	20 5.2%

16. Secondary Outcome

Title	Number of Participants With On-Treatment Laboratory Parameters That Worsened Relative to Baseline
Description	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 10 months and a maximum up to 37 months)

Outcome Measure Data

Analysis Population Description

All treated participants with laboratory baseline measures

Arm/Group Title		Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description:		Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
Overall Number of Participants Analyzed		373	369
Measure Type: Count of Participants; Unit of Measure: Participants
Hemoglobin decreased grade 1-4	Number Analyzed	373 participants	369 participants
		177 47.5%	147 39.8%
Hemoglobin decreased grade 3-4	Number Analyzed	373 participants	369 participants
		12 3.2%	15 4.1%
Platelet count decreased grade 1-4	Number Analyzed	373 participants	369 participants
		29 7.8%	32 8.7%
Platelet count decreased grade 3-4	Number Analyzed	373 participants	369 participants
		2 0.5%	6 1.6%
Leukocytes decreased grade 1-4	Number Analyzed	373 participants	369 participants
		24 6.4%	36 9.8%
Leukocytes decreased grade 3-4	Number Analyzed	373 participants	369 participants
		2 0.5%	0 0.0%
Lymphocytes (absolute) decreased grade 1-4	Number Analyzed	326 participants	319 participants
		64 19.6%	115 36.1%
Lymphocytes (absolute) decreased grade 3-4	Number Analyzed	326 participants	319 participants
		17 5.2%	20 6.3%
Absolute Neutrophil count decreased grade 1-4	Number Analyzed	373 participants	368 participants
		59 15.8%	22 6.0%
Absolute Neutrophil, count decreased grade 3-4	Number Analyzed	373 participants	368 participants
		8 2.1%	1 0.3%
Neutrophils (absolute) decreased grade 1-4	Number Analyzed	373 participants	368 participants
		47 12.6%	20 5.4%
Neutrophils (absolute) decreased grade 3-4	Number Analyzed	373 participants	368 participants
		10 2.7%	1 0.3%
Alkaline Phosphatase increased grade 1-4	Number Analyzed	371 participants	366 participants
		82 22.1%	80 21.9%
Alkaline Phosphatase increased grade 3-4	Number Analyzed	371 participants	366 participants
		2 0.5%	5 1.4%
Aspartate Aminotransferase increased grade 1-4	Number Analyzed	371 participants	369 participants
		82 22.1%	93 25.2%
Aspartate Aminotransferase increased grade 3-4	Number Analyzed	371 participants	369 participants
		9 2.4%	15 4.1%
Alanine Aminotransferase increased grade 1-4	Number Analyzed	372 participants	369 participants
		93 25.0%	113 30.6%
Alanine Aminotransferase increased grade 3-4	Number Analyzed	372 participants	369 participants
		11 3.0%	12 3.3%
Bilirubin, total increased grade 1-4	Number Analyzed	370 participants	368 participants
		31 8.4%	37 10.1%
Bilirubin, total increased grade 3-4	Number Analyzed	370 participants	368 participants
		2 0.5%	4 1.1%
Creatinine increased grade 1-4	Number Analyzed	372 participants	368 participants
		71 19.1%	77 20.9%
Creatinine increased grade 3-4	Number Analyzed	372 participants	368 participants
		2 0.5%	4 1.1%
Amylase increased grade 1-4	Number Analyzed	300 participants	306 participants
		43 14.3%	66 21.6%
Amylase increased grade 3-4	Number Analyzed	300 participants	306 participants
		2 0.7%	4 1.3%
Lipase, total increased grade 1-4	Number Analyzed	347 participants	344 participants
		72 20.7%	104 30.2%
Lipase, total increased grade 3-4	Number Analyzed	347 participants	344 participants
		10 2.9%	14 4.1%
Hypernatremia grade 1-4	Number Analyzed	372 participants	369 participants
		18 4.8%	35 9.5%
Hypernatremia grade 3-4	Number Analyzed	372 participants	369 participants
		0 0.0%	0 0.0%
Hyponatremia grade 1-4	Number Analyzed	372 participants	369 participants
		93 25.0%	105 28.5%
Hyponatremia grade 3-4	Number Analyzed	372 participants	369 participants
		4 1.1%	9 2.4%
Hyperkalemia grade 1-4	Number Analyzed	372 participants	369 participants
		76 20.4%	72 19.5%
Hyperkalemia grade 3-4	Number Analyzed	372 participants	369 participants
		9 2.4%	5 1.4%
Hypokalemia grade 1-4	Number Analyzed	372 participants	369 participants
		24 6.5%	45 12.2%
Hypokalemia grade 3-4	Number Analyzed	372 participants	369 participants
		5 1.3%	2 0.5%
Hypercalcemia grade 1-4	Number Analyzed	365 participants	368 participants
		36 9.9%	32 8.7%
Hypercalcemia grade 3-4	Number Analyzed	365 participants	368 participants
		0 0.0%	0 0.0%
Hypocalcemia grade 1-4	Number Analyzed	365 participants	368 participants
		63 17.3%	63 17.1%
Hypocalcemia grade 3-4	Number Analyzed	365 participants	368 participants
		3 0.8%	0 0.0%
Hypoglycemia grade 1-4	Number Analyzed	368 participants	365 participants
		37 10.1%	33 9.0%
Hypoglycemia grade 3-4	Number Analyzed	368 participants	365 participants
		3 0.8%	0 0.0%

Adverse Events

Time Frame	Adverse Events (AEs) and Serious Adverse Events (SAEs) are collected from first dose to 100 days post last dose (Average of 10 months and a maximum up to 37 months). Participants were assessed for All-cause mortality from their date of randomization to primary completion date (Up to approximately 37 months).
Adverse Event Reporting Description	The number at Risk for All-Cause Mortality=All randomized participants. The number at Risk for SAEs and Other AEs=All treated participants.
Arm/Group Title	Bempegaldesleukin + Nivolumab	Nivolumab
Arm/Group Description	Bempegaldesleukin 0.006 mg/kg IV every 3 weeks + Nivolumab 360 mg IV every 3 weeks	Nivolumab 360 mg IV every 3 weeks
All-Cause Mortality
	Bempegaldesleukin + Nivolumab	Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	105/391 (26.85%)	110/392 (28.06%)
Serious Adverse Events
	Bempegaldesleukin + Nivolumab	Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	144/387 (37.21%)	144/382 (37.70%)
Blood and lymphatic system disorders
Anaemia † 1	3/387 (0.78%)	1/382 (0.26%)
Eosinophilia † 1	3/387 (0.78%)	0/382 (0.00%)
Lymph node haemorrhage † 1	1/387 (0.26%)	0/382 (0.00%)
Lymphadenopathy † 1	0/387 (0.00%)	1/382 (0.26%)
Lymphadenopathy mediastinal † 1	1/387 (0.26%)	0/382 (0.00%)
Pancytopenia † 1	1/387 (0.26%)	0/382 (0.00%)
Thrombocytopenia † 1	0/387 (0.00%)	1/382 (0.26%)
Cardiac disorders
Acute myocardial infarction † 1	1/387 (0.26%)	0/382 (0.00%)
Angina pectoris † 1	2/387 (0.52%)	0/382 (0.00%)
Atrial fibrillation † 1	1/387 (0.26%)	1/382 (0.26%)
Atrial tachycardia † 1	1/387 (0.26%)	0/382 (0.00%)
Bradyarrhythmia † 1	0/387 (0.00%)	1/382 (0.26%)
Cardiac arrest † 1	1/387 (0.26%)	1/382 (0.26%)
Cardiac failure † 1	1/387 (0.26%)	0/382 (0.00%)
Cardio-respiratory arrest † 1	1/387 (0.26%)	0/382 (0.00%)
Cardiovascular disorder † 1	0/387 (0.00%)	1/382 (0.26%)
Myocardial infarction † 1	1/387 (0.26%)	0/382 (0.00%)
Myocarditis † 1	3/387 (0.78%)	5/382 (1.31%)
Pericardial effusion † 1	0/387 (0.00%)	1/382 (0.26%)
Right ventricular failure † 1	1/387 (0.26%)	0/382 (0.00%)
Sinus node dysfunction † 1	1/387 (0.26%)	0/382 (0.00%)
Tachycardia † 1	1/387 (0.26%)	0/382 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	1/387 (0.26%)	0/382 (0.00%)
Hypophysitis † 1	0/387 (0.00%)	1/382 (0.26%)
Hypothyroidism † 1	0/387 (0.00%)	1/382 (0.26%)
Thyroiditis † 1	1/387 (0.26%)	0/382 (0.00%)
Eye disorders
Uveitis † 1	0/387 (0.00%)	1/382 (0.26%)
Gastrointestinal disorders
Abdominal pain † 1	1/387 (0.26%)	2/382 (0.52%)
Abdominal pain upper † 1	0/387 (0.00%)	1/382 (0.26%)
Abdominal wall haematoma † 1	1/387 (0.26%)	0/382 (0.00%)
Ascites † 1	0/387 (0.00%)	3/382 (0.79%)
Autoimmune colitis † 1	3/387 (0.78%)	2/382 (0.52%)
Autoimmune pancreatitis † 1	0/387 (0.00%)	2/382 (0.52%)
Colitis † 1	2/387 (0.52%)	3/382 (0.79%)
Constipation † 1	1/387 (0.26%)	2/382 (0.52%)
Diarrhoea † 1	3/387 (0.78%)	5/382 (1.31%)
Dysphagia † 1	2/387 (0.52%)	0/382 (0.00%)
Gastric ulcer † 1	1/387 (0.26%)	0/382 (0.00%)
Gastritis † 1	1/387 (0.26%)	0/382 (0.00%)
Gastrointestinal haemorrhage † 1	0/387 (0.00%)	1/382 (0.26%)
Haemorrhoidal haemorrhage † 1	0/387 (0.00%)	1/382 (0.26%)
Immune-mediated enterocolitis † 1	1/387 (0.26%)	2/382 (0.52%)
Inguinal hernia † 1	0/387 (0.00%)	1/382 (0.26%)
Intestinal obstruction † 1	1/387 (0.26%)	0/382 (0.00%)
Intestinal perforation † 1	1/387 (0.26%)	0/382 (0.00%)
Nausea † 1	0/387 (0.00%)	1/382 (0.26%)
Obstructive pancreatitis † 1	1/387 (0.26%)	0/382 (0.00%)
Pancreatitis † 1	1/387 (0.26%)	2/382 (0.52%)
Pancreatitis acute † 1	1/387 (0.26%)	0/382 (0.00%)
Upper gastrointestinal haemorrhage † 1	1/387 (0.26%)	0/382 (0.00%)
Vomiting † 1	1/387 (0.26%)	1/382 (0.26%)
General disorders
Asthenia † 1	0/387 (0.00%)	1/382 (0.26%)
Chest pain † 1	1/387 (0.26%)	0/382 (0.00%)
Condition aggravated † 1	1/387 (0.26%)	0/382 (0.00%)
Death † 1	0/387 (0.00%)	1/382 (0.26%)
Disease progression † 1	2/387 (0.52%)	1/382 (0.26%)
Drowning † 1	1/387 (0.26%)	0/382 (0.00%)
Face oedema † 1	2/387 (0.52%)	0/382 (0.00%)
Fatigue † 1	2/387 (0.52%)	3/382 (0.79%)
General physical health deterioration † 1	3/387 (0.78%)	1/382 (0.26%)
Implant site haemorrhage † 1	1/387 (0.26%)	0/382 (0.00%)
Localised oedema † 1	1/387 (0.26%)	0/382 (0.00%)
Mucosal inflammation † 1	1/387 (0.26%)	0/382 (0.00%)
Non-cardiac chest pain † 1	1/387 (0.26%)	0/382 (0.00%)
Pain † 1	1/387 (0.26%)	0/382 (0.00%)
Pyrexia † 1	2/387 (0.52%)	4/382 (1.05%)
Sudden death † 1	0/387 (0.00%)	2/382 (0.52%)
Systemic inflammatory response syndrome † 1	1/387 (0.26%)	0/382 (0.00%)
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/387 (0.00%)	1/382 (0.26%)
Biliary obstruction † 1	1/387 (0.26%)	0/382 (0.00%)
Cholangitis † 1	0/387 (0.00%)	1/382 (0.26%)
Cholestasis † 1	1/387 (0.26%)	0/382 (0.00%)
Hepatic cytolysis † 1	1/387 (0.26%)	1/382 (0.26%)
Hepatic failure † 1	1/387 (0.26%)	0/382 (0.00%)
Portal vein thrombosis † 1	0/387 (0.00%)	1/382 (0.26%)
Immune system disorders
Anaphylactic reaction † 1	1/387 (0.26%)	0/382 (0.00%)
Anaphylactic shock † 1	1/387 (0.26%)	1/382 (0.26%)
Contrast media allergy † 1	1/387 (0.26%)	0/382 (0.00%)
Cytokine release syndrome † 1	1/387 (0.26%)	0/382 (0.00%)
Sarcoidosis † 1	0/387 (0.00%)	1/382 (0.26%)
Infections and infestations
Bacteraemia † 1	0/387 (0.00%)	1/382 (0.26%)
Bacterial infection † 1	0/387 (0.00%)	1/382 (0.26%)
Biliary tract infection † 1	1/387 (0.26%)	0/382 (0.00%)
COVID-19 † 1	2/387 (0.52%)	4/382 (1.05%)
COVID-19 pneumonia † 1	0/387 (0.00%)	1/382 (0.26%)
Cellulitis † 1	2/387 (0.52%)	0/382 (0.00%)
Cystitis † 1	0/387 (0.00%)	1/382 (0.26%)
Diverticulitis † 1	0/387 (0.00%)	1/382 (0.26%)
Encephalitis † 1	1/387 (0.26%)	0/382 (0.00%)
Erysipelas † 1	1/387 (0.26%)	0/382 (0.00%)
Gastroenteritis † 1	2/387 (0.52%)	0/382 (0.00%)
Herpes zoster † 1	0/387 (0.00%)	1/382 (0.26%)
Infection † 1	2/387 (0.52%)	1/382 (0.26%)
Influenza † 1	1/387 (0.26%)	0/382 (0.00%)
Meningitis bacterial † 1	0/387 (0.00%)	1/382 (0.26%)
Orchitis † 1	1/387 (0.26%)	0/382 (0.00%)
Osteomyelitis † 1	1/387 (0.26%)	0/382 (0.00%)
Periorbital cellulitis † 1	0/387 (0.00%)	1/382 (0.26%)
Peritonitis † 1	0/387 (0.00%)	1/382 (0.26%)
Pneumonia † 1	3/387 (0.78%)	7/382 (1.83%)
Pneumonia aspiration † 1	0/387 (0.00%)	1/382 (0.26%)
Pneumonia bacterial † 1	0/387 (0.00%)	1/382 (0.26%)
Sepsis † 1	5/387 (1.29%)	2/382 (0.52%)
Septic shock † 1	1/387 (0.26%)	1/382 (0.26%)
Severe acute respiratory syndrome † 1	0/387 (0.00%)	1/382 (0.26%)
Skin infection † 1	3/387 (0.78%)	0/382 (0.00%)
Soft tissue infection † 1	1/387 (0.26%)	1/382 (0.26%)
Tonsillitis bacterial † 1	1/387 (0.26%)	0/382 (0.00%)
Upper respiratory tract infection † 1	1/387 (0.26%)	0/382 (0.00%)
Urinary tract infection † 1	2/387 (0.52%)	1/382 (0.26%)
Urinary tract infection bacterial † 1	0/387 (0.00%)	1/382 (0.26%)
Urosepsis † 1	1/387 (0.26%)	2/382 (0.52%)
Injury, poisoning and procedural complications
Femoral neck fracture † 1	1/387 (0.26%)	0/382 (0.00%)
Head injury † 1	0/387 (0.00%)	1/382 (0.26%)
Infusion related reaction † 1	2/387 (0.52%)	0/382 (0.00%)
Post procedural haemorrhage † 1	0/387 (0.00%)	1/382 (0.26%)
Postoperative ileus † 1	0/387 (0.00%)	1/382 (0.26%)
Spinal fracture † 1	1/387 (0.26%)	0/382 (0.00%)
Subdural haematoma † 1	1/387 (0.26%)	1/382 (0.26%)
Thoracic vertebral fracture † 1	0/387 (0.00%)	1/382 (0.26%)
Toxicity to various agents † 1	0/387 (0.00%)	1/382 (0.26%)
Vaccination complication † 1	0/387 (0.00%)	1/382 (0.26%)
Wrist fracture † 1	1/387 (0.26%)	0/382 (0.00%)
Investigations
Alanine aminotransferase increased † 1	2/387 (0.52%)	1/382 (0.26%)
Aspartate aminotransferase increased † 1	3/387 (0.78%)	1/382 (0.26%)
Blood creatinine increased † 1	1/387 (0.26%)	1/382 (0.26%)
Lipase decreased † 1	0/387 (0.00%)	1/382 (0.26%)
Lipase increased † 1	0/387 (0.00%)	2/382 (0.52%)
Liver function test increased † 1	1/387 (0.26%)	1/382 (0.26%)
Lymph node palpable † 1	1/387 (0.26%)	0/382 (0.00%)
Troponin increased † 1	0/387 (0.00%)	1/382 (0.26%)
Metabolism and nutrition disorders
Decreased appetite † 1	1/387 (0.26%)	0/382 (0.00%)
Dehydration † 1	1/387 (0.26%)	1/382 (0.26%)
Diabetic ketoacidosis † 1	1/387 (0.26%)	1/382 (0.26%)
Hyperglycaemia † 1	0/387 (0.00%)	1/382 (0.26%)
Hypokalaemia † 1	0/387 (0.00%)	1/382 (0.26%)
Hyponatraemia † 1	3/387 (0.78%)	2/382 (0.52%)
Metabolic acidosis † 1	1/387 (0.26%)	1/382 (0.26%)
Tumour lysis syndrome † 1	0/387 (0.00%)	1/382 (0.26%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/387 (0.26%)	2/382 (0.52%)
Back pain † 1	2/387 (0.52%)	1/382 (0.26%)
Groin pain † 1	2/387 (0.52%)	0/382 (0.00%)
Morphoea † 1	0/387 (0.00%)	1/382 (0.26%)
Muscular weakness † 1	0/387 (0.00%)	2/382 (0.52%)
Musculoskeletal pain † 1	1/387 (0.26%)	0/382 (0.00%)
Myositis † 1	1/387 (0.26%)	5/382 (1.31%)
Pain in extremity † 1	2/387 (0.52%)	1/382 (0.26%)
Spinal stenosis † 1	1/387 (0.26%)	1/382 (0.26%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/387 (0.26%)	1/382 (0.26%)
Cancer pain † 1	0/387 (0.00%)	3/382 (0.79%)
Gastrointestinal stromal tumour † 1	1/387 (0.26%)	0/382 (0.00%)
Infected neoplasm † 1	0/387 (0.00%)	1/382 (0.26%)
Intestinal metastasis † 1	0/387 (0.00%)	1/382 (0.26%)
Malignant melanoma † 1	0/387 (0.00%)	2/382 (0.52%)
Malignant neoplasm progression † 1	30/387 (7.75%)	36/382 (9.42%)
Malignant pleural effusion † 1	2/387 (0.52%)	0/382 (0.00%)
Metastases to central nervous system † 1	0/387 (0.00%)	3/382 (0.79%)
Metastases to lymph nodes † 1	1/387 (0.26%)	0/382 (0.00%)
Metastases to meninges † 1	0/387 (0.00%)	1/382 (0.26%)
Metastatic malignant melanoma † 1	1/387 (0.26%)	0/382 (0.00%)
Metastatic neoplasm † 1	0/387 (0.00%)	1/382 (0.26%)
Neoplasm † 1	0/387 (0.00%)	1/382 (0.26%)
Oncologic complication † 1	0/387 (0.00%)	1/382 (0.26%)
Squamous cell carcinoma † 1	0/387 (0.00%)	1/382 (0.26%)
Tumour pain † 1	0/387 (0.00%)	1/382 (0.26%)
Nervous system disorders
Cerebral haemorrhage † 1	1/387 (0.26%)	1/382 (0.26%)
Cerebral infarction † 1	1/387 (0.26%)	0/382 (0.00%)
Cerebrovascular accident † 1	6/387 (1.55%)	1/382 (0.26%)
Dizziness † 1	1/387 (0.26%)	0/382 (0.00%)
Encephalitis autoimmune † 1	0/387 (0.00%)	2/382 (0.52%)
Encephalopathy † 1	1/387 (0.26%)	0/382 (0.00%)
Facial paralysis † 1	1/387 (0.26%)	0/382 (0.00%)
Guillain-Barre syndrome † 1	1/387 (0.26%)	0/382 (0.00%)
Haemorrhage intracranial † 1	1/387 (0.26%)	1/382 (0.26%)
Headache † 1	0/387 (0.00%)	1/382 (0.26%)
Ischaemic stroke † 1	1/387 (0.26%)	4/382 (1.05%)
Myasthenia gravis † 1	0/387 (0.00%)	1/382 (0.26%)
Paraesthesia † 1	0/387 (0.00%)	1/382 (0.26%)
Polyneuropathy † 1	1/387 (0.26%)	0/382 (0.00%)
Presyncope † 1	0/387 (0.00%)	1/382 (0.26%)
Seizure † 1	1/387 (0.26%)	3/382 (0.79%)
Spinal cord compression † 1	1/387 (0.26%)	3/382 (0.79%)
Syncope † 1	2/387 (0.52%)	1/382 (0.26%)
Transient ischaemic attack † 1	1/387 (0.26%)	0/382 (0.00%)
Psychiatric disorders
Adjustment disorder † 1	1/387 (0.26%)	0/382 (0.00%)
Confusional state † 1	0/387 (0.00%)	1/382 (0.26%)
Renal and urinary disorders
Acute kidney injury † 1	7/387 (1.81%)	3/382 (0.79%)
Autoimmune nephritis † 1	0/387 (0.00%)	2/382 (0.52%)
Hydronephrosis † 1	1/387 (0.26%)	0/382 (0.00%)
Renal colic † 1	0/387 (0.00%)	1/382 (0.26%)
Renal failure † 1	1/387 (0.26%)	0/382 (0.00%)
Reproductive system and breast disorders
Prostatitis † 1	1/387 (0.26%)	0/382 (0.00%)
Testicular mass † 1	1/387 (0.26%)	0/382 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/387 (0.00%)	1/382 (0.26%)
Alveolitis † 1	0/387 (0.00%)	1/382 (0.26%)
Asthma-chronic obstructive pulmonary disease overlap syndrome † 1	1/387 (0.26%)	0/382 (0.00%)
Autoimmune lung disease † 1	1/387 (0.26%)	0/382 (0.00%)
Bronchospasm † 1	0/387 (0.00%)	1/382 (0.26%)
Chronic obstructive pulmonary disease † 1	1/387 (0.26%)	1/382 (0.26%)
Dyspnoea † 1	2/387 (0.52%)	1/382 (0.26%)
Haemoptysis † 1	0/387 (0.00%)	1/382 (0.26%)
Laryngeal polyp † 1	0/387 (0.00%)	1/382 (0.26%)
Pleural effusion † 1	3/387 (0.78%)	1/382 (0.26%)
Pneumonitis † 1	2/387 (0.52%)	1/382 (0.26%)
Pulmonary embolism † 1	5/387 (1.29%)	2/382 (0.52%)
Respiratory failure † 1	2/387 (0.52%)	2/382 (0.52%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised † 1	1/387 (0.26%)	0/382 (0.00%)
Immune-mediated dermatitis † 1	1/387 (0.26%)	0/382 (0.00%)
Ingrowing nail † 1	1/387 (0.26%)	0/382 (0.00%)
Pain of skin † 1	1/387 (0.26%)	0/382 (0.00%)
Rash † 1	2/387 (0.52%)	0/382 (0.00%)
Skin lesion † 1	1/387 (0.26%)	0/382 (0.00%)
Surgical and medical procedures
Rotator cuff repair † 1	0/387 (0.00%)	1/382 (0.26%)
Vascular disorders
Arterial occlusive disease † 1	0/387 (0.00%)	1/382 (0.26%)
Deep vein thrombosis † 1	1/387 (0.26%)	1/382 (0.26%)
Embolism † 1	1/387 (0.26%)	0/382 (0.00%)
Hypotension † 1	3/387 (0.78%)	1/382 (0.26%)
Ischaemia † 1	0/387 (0.00%)	1/382 (0.26%)
Shock haemorrhagic † 1	0/387 (0.00%)	1/382 (0.26%)
1 Term from vocabulary, 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bempegaldesleukin + Nivolumab	Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	350/387 (90.44%)	313/382 (81.94%)
Blood and lymphatic system disorders
Anaemia † 1	54/387 (13.95%)	56/382 (14.66%)
Eosinophilia † 1	51/387 (13.18%)	6/382 (1.57%)
Endocrine disorders
Hyperthyroidism † 1	48/387 (12.40%)	26/382 (6.81%)
Hypothyroidism † 1	70/387 (18.09%)	45/382 (11.78%)
Gastrointestinal disorders
Abdominal pain † 1	27/387 (6.98%)	26/382 (6.81%)
Abdominal pain upper † 1	23/387 (5.94%)	11/382 (2.88%)
Constipation † 1	31/387 (8.01%)	46/382 (12.04%)
Diarrhoea † 1	83/387 (21.45%)	72/382 (18.85%)
Nausea † 1	102/387 (26.36%)	57/382 (14.92%)
Vomiting † 1	57/387 (14.73%)	31/382 (8.12%)
General disorders
Asthenia † 1	60/387 (15.50%)	36/382 (9.42%)
Chills † 1	34/387 (8.79%)	4/382 (1.05%)
Fatigue † 1	120/387 (31.01%)	95/382 (24.87%)
Influenza like illness † 1	69/387 (17.83%)	7/382 (1.83%)
Oedema peripheral † 1	39/387 (10.08%)	27/382 (7.07%)
Pyrexia † 1	143/387 (36.95%)	34/382 (8.90%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	48/387 (12.40%)	15/382 (3.93%)
Investigations
Alanine aminotransferase increased † 1	29/387 (7.49%)	36/382 (9.42%)
Amylase increased † 1	17/387 (4.39%)	27/382 (7.07%)
Aspartate aminotransferase increased † 1	24/387 (6.20%)	28/382 (7.33%)
Blood creatine phosphokinase increased † 1	18/387 (4.65%)	29/382 (7.59%)
Blood creatinine increased † 1	14/387 (3.62%)	21/382 (5.50%)
Lipase increased † 1	18/387 (4.65%)	30/382 (7.85%)
Metabolism and nutrition disorders
Decreased appetite † 1	58/387 (14.99%)	28/382 (7.33%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	83/387 (21.45%)	53/382 (13.87%)
Back pain † 1	30/387 (7.75%)	34/382 (8.90%)
Myalgia † 1	50/387 (12.92%)	25/382 (6.54%)
Pain in extremity † 1	30/387 (7.75%)	31/382 (8.12%)
Nervous system disorders
Dizziness † 1	37/387 (9.56%)	12/382 (3.14%)
Headache † 1	58/387 (14.99%)	47/382 (12.30%)
Psychiatric disorders
Insomnia † 1	28/387 (7.24%)	18/382 (4.71%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	46/387 (11.89%)	38/382 (9.95%)
Dyspnoea † 1	29/387 (7.49%)	25/382 (6.54%)
Skin and subcutaneous tissue disorders
Dry skin † 1	26/387 (6.72%)	12/382 (3.14%)
Erythema † 1	27/387 (6.98%)	7/382 (1.83%)
Pruritus † 1	114/387 (29.46%)	65/382 (17.02%)
Rash † 1	99/387 (25.58%)	51/382 (13.35%)
Rash maculo-papular † 1	27/387 (6.98%)	14/382 (3.66%)
Vitiligo † 1	25/387 (6.46%)	24/382 (6.28%)
Vascular disorders
Hypertension † 1	22/387 (5.68%)	23/382 (6.02%)
Hypotension † 1	33/387 (8.53%)	4/382 (1.05%)
1 Term from vocabulary, 24.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please Email
• EMail: Clinical.Trials@bms.com

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

Khushalani NI, Diab A, Ascierto PA, Larkin J, Sandhu S, Sznol M, Koon HB, Jarkowski A, Zhou M, Statkevich P, Geese WJ, Long GV. Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. Future Oncol. 2020 Oct;16(28):2165-2175. doi: 10.2217/fon-2020-0351. Epub 2020 Jul 29.

• 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 Submitted: August 16, 2018
• First Posted: August 17, 2018
• Results First Submitted: November 18, 2022
• Results First Posted: December 19, 2022
• Last Update Posted: October 18, 2023