A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)

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ClinicalTrials.gov Identifier: NCT03729245

Recruitment Status : Terminated (Sponsor decision)

First Posted : November 2, 2018

Results First Posted : April 11, 2023

Last Update Posted : April 11, 2023

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by (Responsible Party):

Nektar Therapeutics

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Renal Cell Carcinoma Metastatic Renal Cell Carcinoma
Interventions	Biological: bempegaldesleukin Drug: sunitinib Biological: nivolumab Drug: cabozantinib
Enrollment	623

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
Arm/Group Description	Patients in Arm A will receive bemp...	Patients in Arm B will receive the ...
Arm/Group Description	Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w	Patients in Arm B will receive the Investigator's choice of either one of two treatment options. Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily
Period Title: Overall Study
Started	311	312
Completed	289	287
Not Completed	22	25
Reason Not Completed
Lost to Follow-up	5	6
Withdrawal by Subject	16	19
Patient did not complete the end of study form but is not followed on the study anymore.	1	0

Baseline Characteristics

Arm/Group Title		Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib	Total
Arm/Group Description		Patients in Arm A will receive bemp...	Patients in Arm B will receive the ...	Total of all reporting groups
Arm/Group Description		Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w	Patients in Arm B will receive the Investigator's choice of either one of two treatment options. Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily	Total of all reporting groups
Overall Number of Baseline Participants		311	312	623
Baseline Analysis Population Description		...
Baseline Analysis Population Description		A total of 623 patients were randomized in the ITT International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) All-risk population, including 514 patients for the ITT I/P-risk population: NKTR-214/nivolumab: 311 and 256, respectively Sunitinib or cabozantinib: 312 and 258, respectively
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	311 participants	312 participants	623 participants
		61.5 (9.74)	60.8 (10.24)	61.2 (9.99)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	311 participants	312 participants	623 participants
	Female	75 24.1%	80 25.6%	155 24.9%
	Male	236 75.9%	232 74.4%	468 75.1%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	311 participants	312 participants	623 participants
	Hispanic or Latino	148 47.6%	131 42.0%	279 44.8%
	Not Hispanic or Latino	157 50.5%	172 55.1%	329 52.8%
	Unknown or Not Reported	6 1.9%	9 2.9%	15 2.4%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	311 participants	312 participants	623 participants
White		271 87.1%	272 87.2%	543 87.2%
Black or African American		7 2.3%	6 1.9%	13 2.1%
Asian		5 1.6%	7 2.2%	12 1.9%
American Indian or Alaska Native		14 4.5%	8 2.6%	22 3.5%
Native Hawaiian or Other Pacific Islander		0 0.0%	0 0.0%	0 0.0%
Not Reported		7 2.3%	8 2.6%	15 2.4%
Other		7 2.3%	11 3.5%	18 2.9%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	311 participants	312 participants	623 participants
Argentina		49 15.8%	28 9.0%	77 12.4%
Singapore		3 1.0%	2 0.6%	5 0.8%
United States		41 13.2%	50 16.0%	91 14.6%
Russia		95 30.5%	108 34.6%	203 32.6%
New Zealand		4 1.3%	2 0.6%	6 1.0%
Brazil		68 21.9%	82 26.3%	150 24.1%
Mexico		16 5.1%	11 3.5%	27 4.3%
Australia		7 2.3%	8 2.6%	15 2.4%
Chile		19 6.1%	16 5.1%	35 5.6%
Peru		9 2.9%	5 1.6%	14 2.2%
Karnofsky Performance Status (KPS) Score ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	311 participants	312 participants	623 participants
KPS < 80		77	75	152
KPS >= 80		234	237	471
		[1] Measure Description: The Karnofsky Performance Status (KPS) scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities; For example: Score of 100 = Normal, no complaints, no evidence of disease. 80 = Normal activity with effort; some signs or symptoms of disease. 50 = Requires considerable assistance and frequent medical care. 30 = Severely disabled, hospitalization indicated. Death not imminent. 0 = Dead

Outcome Measures

1.Primary Outcome


Title	Objective Response Rate (ORR) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC
Description	ORR using modified Response Evaluation Criteria in Solid Tumors (mRECI...
Description	ORR using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1 by Blinded Independent Central Review (BICR) in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) All-risk patients and intermediate- or poor-risk patients. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.
Time Frame	Approximately 32 months

Outcome Measure Data

Analysis Population Description

A total of 623 patients randomized in the ITT All-risk population, including 514 patients for the ITT I/P-risk population:

NKTR-214/nivolumab: 311 (ITT All-risk population) and 256 (ITT I/P-risk population), respectively
Sunitinib or Cabozantinib (TKI): 312 (ITT All-risk population) and 258 (ITT I/P-risk population), respectively


Arm/Group Title		Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
Arm/Group Description:		Patients in Arm A will receive bemp...	Patients in Arm B will receive the ...
Arm/Group Description:		Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w	Patients in Arm B will receive the Investigator's choice of either one of two treatment options. Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily
Overall Number of Participants Analyzed		311	312
Measure Type: Count of Participants Unit of Measure: Participants
ORR per mRECIST 1.1 by BICR, ITT All-risk population	Number Analyzed	311 participants	312 participants
ORR per mRECIST 1.1 by BICR, ITT All-risk population		73 23.5%	109 34.9%
ORR per mRECIST 1.1 by BICR, ITT I/P-risk population	Number Analyzed	256 participants	258 participants
ORR per mRECIST 1.1 by BICR, ITT I/P-risk population		59 23.0%	79 30.6%

2.Primary Outcome


Title	Overall Survival (OS) in IMDC All-Risk and Intermediate- or Poor-risk Patients With Previously Untreated Advanced RCC
Description	OS is defined as the time from date of first dose to the date of death...
Description	OS is defined as the time from date of first dose to the date of death from any cause. Patients without a date of death were censored at their last known alive date.
Time Frame	Approximately 32 months

Outcome Measure Data

Analysis Population Description

A total of 623 patients randomized in the ITT All-risk population, including 514 patients for the ITT I/P-risk population:

NKTR-214/nivolumab: 311 (ITT All-risk population) and 256 (ITT I/P-risk population), respectively
Sunitinib or Cabozantinib (TKI): 312 (ITT All-risk population) and 258 (ITT I/P-risk population), respectively


Arm/Group Title		Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
Arm/Group Description:		Patients in Arm A will receive bemp...	Patients in Arm B will receive the ...
Arm/Group Description:		Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w	Patients in Arm B will receive the Investigator's choice of either one of two treatment options. Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily
Overall Number of Participants Analyzed		311	312
Median (95% Confidence Interval) Unit of Measure: months
OS, ITT All-risk population	Number Analyzed	311 participants	312 participants
OS, ITT All-risk population		NA ^[1] (29.0 to NA)	NA ^[2] (NA to NA)
OS, ITT I/P-risk population	Number Analyzed	256 participants	258 participants
OS, ITT I/P-risk population		29 ^[3] (25.6 to NA)	NA ^[1] (25.6 to NA)

[1]

Median and upper CI was not estimable due to insufficient number of events.

[2]

Median and 95% CI was not estimable due to insufficient number of events.

[3]

Upper CI was not estimable due to insufficient number of events.

3.Secondary Outcome


Title	Progression Free Survival (PFS) Per mRECIST 1.1 by BICR in IMDC All-risk Patients and Intermediate- or Poor (I/P)-Risk Patients With Previously Untreated Advanced RCC
Description	Progression-free survival is defined as the time between the date of r...
Description	Progression-free survival is defined as the time between the date of randomization and the first date of documented tumor progression using mRECIST 1.1 per BICR or death due to any cause, whichever comes first.
Time Frame	Approximately 32 months

Outcome Measure Data

Analysis Population Description

A total of 623 patients randomized in the ITT All-risk population, including 514 patients for the ITT I/P-risk population:

NKTR-214/nivolumab: 311 (ITT All-risk population) and 256 (ITT I/P-risk population), respectively
Sunitinib or Cabozantinib (TKI): 312 (ITT All-risk population) and 258 (ITT I/P-risk population), respectively


Arm/Group Title		Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
Arm/Group Description:		Patients in Arm A will receive bemp...	Patients in Arm B will receive the ...
Arm/Group Description:		Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w	Patients in Arm B will receive the Investigator's choice of either one of two treatment options. Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily
Overall Number of Participants Analyzed		311	312
Median (95% Confidence Interval) Unit of Measure: Months
PFS per mRECIST 1.1. by BICR, ITT All-risk population	Number Analyzed	311 participants	312 participants
PFS per mRECIST 1.1. by BICR, ITT All-risk population		8.2 (6.2 to 10.0)	10.3 (8.5 to 12.4)
PFS per mRECIST 1.1. by BICR, ITT I/P-risk population	Number Analyzed	256 participants	258 participants
PFS per mRECIST 1.1. by BICR, ITT I/P-risk population		6.4 (4.6 to 8.3)	9.2 (8.3 to 12.2)

Adverse Events

Time Frame	AEs will be reported starting immediately after the patient has been administered the first dose of study drug(s) until 100 days after the last dose of all study drug(s), up to 38 months. All ongoing non-serious AEs will be followed until resolution, the patient is lost to follow-up, patient death, or until the last Safety Follow-Up Visit. If the AE has not completely resolved by the last Safety Follow-Up Visit, the final outcome of these ongoing AEs will be captured.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
Arm/Group Description	Patients in Arm A will receive bemp...	Patients in Arm B will receive the ...
Arm/Group Description	Patients in Arm A will receive bempegaldesleukin in combination with nivolumab. Bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) every 3 weeks (q3w) combined with nivolumab 360 mg IV q3w	Patients in Arm B will receive the Investigator's choice of either one of two treatment options. Sunitinib 50 mg per orally (po) once daily for 4 weeks followed by 2 weeks off OR Cabozantinib 60 mg po once daily
All-Cause Mortality
	Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	109/310 (35.16%)	114/306 (37.25%)
Serious Adverse Events Serious Adverse Events
	Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	113/310 (36.45%)	91/306 (29.74%)
Blood and lymphatic system disorders
Anaemia ^* 1	3/310 (0.97%)	5/306 (1.63%)
Eosinophilia ^* 1	2/310 (0.65%)	0/306 (0.00%)
Thrombocytopenia ^* 1	0/310 (0.00%)	2/306 (0.65%)
Anaemia of chronic disease ^* 1	0/310 (0.00%)	1/306 (0.33%)
Febrile neutropenia ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hypereosinophilic syndrome ^* 1	1/310 (0.32%)	0/306 (0.00%)
Cardiac disorders
Cardiac arrest ^* 1	2/310 (0.65%)	2/306 (0.65%)
Acute coronary syndrome ^* 1	2/310 (0.65%)	1/306 (0.33%)
Angina pectoris ^* 1	1/310 (0.32%)	2/306 (0.65%)
Atrial fibrillation ^* 1	2/310 (0.65%)	1/306 (0.33%)
Cardiac failure ^* 1	2/310 (0.65%)	1/306 (0.33%)
Cardio-respiratory arrest ^* 1	2/310 (0.65%)	1/306 (0.33%)
Acute myocardial infarction ^* 1	2/310 (0.65%)	0/306 (0.00%)
Cardiac failure acute ^* 1	0/310 (0.00%)	1/306 (0.33%)
Cardiogenic shock ^* 1	1/310 (0.32%)	0/306 (0.00%)
Coronary artery disease ^* 1	0/310 (0.00%)	1/306 (0.33%)
Mitral valve incompetence ^* 1	0/310 (0.00%)	1/306 (0.33%)
Myocardial infarction ^* 1	1/310 (0.32%)	0/306 (0.00%)
Ventricular tachycardia ^* 1	1/310 (0.32%)	0/306 (0.00%)
Endocrine disorders
Adrenal insufficiency ^* 1	2/310 (0.65%)	0/306 (0.00%)
Autoimmune thyroiditis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Eye disorders
Retinal vein occlusion ^* 1	1/310 (0.32%)	0/306 (0.00%)
Gastrointestinal disorders
Abdominal pain ^* 1	3/310 (0.97%)	2/306 (0.65%)
Diarrhoea ^* 1	3/310 (0.97%)	1/306 (0.33%)
Colitis ^* 1	1/310 (0.32%)	2/306 (0.65%)
Gastrointestinal haemorrhage ^* 1	2/310 (0.65%)	1/306 (0.33%)
Pancreatitis acute ^* 1	1/310 (0.32%)	2/306 (0.65%)
Ascites ^* 1	2/310 (0.65%)	0/306 (0.00%)
Anal fistula ^* 1	0/310 (0.00%)	1/306 (0.33%)
Colonic fistula ^* 1	0/310 (0.00%)	1/306 (0.33%)
Diverticular perforation ^* 1	0/310 (0.00%)	1/306 (0.33%)
Duodenal perforation ^* 1	1/310 (0.32%)	0/306 (0.00%)
Erosive oesophagitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Gastric perforation ^* 1	1/310 (0.32%)	0/306 (0.00%)
Gastrointestinal polyp haemorrhage ^* 1	1/310 (0.32%)	0/306 (0.00%)
Haemorrhagic erosive gastritis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Intestinal haemorrhage ^* 1	1/310 (0.32%)	0/306 (0.00%)
Intestinal perforation ^* 1	1/310 (0.32%)	0/306 (0.00%)
Large intestinal haemorrhage ^* 1	0/310 (0.00%)	1/306 (0.33%)
Oesophagitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Oesophagitis haemorrhagic ^* 1	0/310 (0.00%)	1/306 (0.33%)
Proctitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Rectal haemorrhage ^* 1	1/310 (0.32%)	0/306 (0.00%)
Small intestinal haemorrhage ^* 1	1/310 (0.32%)	0/306 (0.00%)
Stomatitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Vomiting ^* 1	1/310 (0.32%)	0/306 (0.00%)
General disorders
Fatigue ^* 1	2/310 (0.65%)	1/306 (0.33%)
Generalised oedema ^* 1	2/310 (0.65%)	1/306 (0.33%)
Pyrexia ^* 1	2/310 (0.65%)	1/306 (0.33%)
Asthenia ^* 1	2/310 (0.65%)	0/306 (0.00%)
Multiple organ dysfunction syndrome ^* 1	1/310 (0.32%)	1/306 (0.33%)
Chest pain ^* 1	1/310 (0.32%)	0/306 (0.00%)
Death ^* 1	0/310 (0.00%)	1/306 (0.33%)
General physical health deterioration ^* 1	1/310 (0.32%)	0/306 (0.00%)
Influenza like illness ^* 1	1/310 (0.32%)	0/306 (0.00%)
Pain ^* 1	1/310 (0.32%)	0/306 (0.00%)
Sudden death ^* 1	1/310 (0.32%)	0/306 (0.00%)
Hepatobiliary disorders
Cholangitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Cholelithiasis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hepatic failure ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hepatitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Jaundice ^* 1	0/310 (0.00%)	1/306 (0.33%)
Portal vein thrombosis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Immune system disorders
Anaphylactic reaction ^* 1	1/310 (0.32%)	0/306 (0.00%)
Contrast media allergy ^* 1	1/310 (0.32%)	0/306 (0.00%)
Contrast media reaction ^* 1	1/310 (0.32%)	0/306 (0.00%)
Infections and infestations
Corona virus infection ^* 1	13/310 (4.19%)	3/306 (0.98%)
Pneumonia ^* 1	9/310 (2.90%)	2/306 (0.65%)
Pneumonia viral ^* 1	4/310 (1.29%)	2/306 (0.65%)
Sepsis ^* 1	4/310 (1.29%)	1/306 (0.33%)
Respiratory tract infection ^* 1	1/310 (0.32%)	2/306 (0.65%)
Urinary tract infection ^* 1	1/310 (0.32%)	2/306 (0.65%)
Infection ^* 1	1/310 (0.32%)	1/306 (0.33%)
Anal abscess ^* 1	0/310 (0.00%)	1/306 (0.33%)
Appendicitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Atypical pneumonia ^* 1	1/310 (0.32%)	0/306 (0.00%)
Bronchitis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Cellulitis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Diverticulitis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Endotoxic shock ^* 1	1/310 (0.32%)	0/306 (0.00%)
Liver abscess ^* 1	1/310 (0.32%)	0/306 (0.00%)
Osteomyelitis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Osteomyelitis chronic ^* 1	0/310 (0.00%)	1/306 (0.33%)
Parotid abscess ^* 1	0/310 (0.00%)	1/306 (0.33%)
Pharyngitis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Postoperative wound infection ^* 1	0/310 (0.00%)	1/306 (0.33%)
Pulmonary sepsis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Pyelonephritis chronic ^* 1	0/310 (0.00%)	1/306 (0.33%)
Subcutaneous abscess ^* 1	0/310 (0.00%)	1/306 (0.33%)
Tonsillitis bacterial ^* 1	1/310 (0.32%)	0/306 (0.00%)
Injury, poisoning and procedural complications
Infusion related reaction ^* 1	3/310 (0.97%)	0/306 (0.00%)
Clavicle fracture ^* 1	0/310 (0.00%)	2/306 (0.65%)
Hip fracture ^* 1	1/310 (0.32%)	1/306 (0.33%)
Fall ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hand fracture ^* 1	0/310 (0.00%)	1/306 (0.33%)
Joint dislocation ^* 1	1/310 (0.32%)	0/306 (0.00%)
Skull fractured base ^* 1	0/310 (0.00%)	1/306 (0.33%)
Thoracic vertebral fracture ^* 1	0/310 (0.00%)	1/306 (0.33%)
Wound dehiscence ^* 1	0/310 (0.00%)	1/306 (0.33%)
Investigations
Blood creatinine increased ^* 1	2/310 (0.65%)	0/306 (0.00%)
Blood creatine phosphokinase increased ^* 1	1/310 (0.32%)	0/306 (0.00%)
Ejection fraction decreased ^* 1	1/310 (0.32%)	0/306 (0.00%)
Metabolism and nutrition disorders
Hypercalcaemia ^* 1	2/310 (0.65%)	2/306 (0.65%)
Hyponatraemia ^* 1	3/310 (0.97%)	1/306 (0.33%)
Dehydration ^* 1	2/310 (0.65%)	1/306 (0.33%)
Hypokalaemia ^* 1	1/310 (0.32%)	1/306 (0.33%)
Decreased appetite ^* 1	1/310 (0.32%)	0/306 (0.00%)
Diabetes mellitus ^* 1	1/310 (0.32%)	0/306 (0.00%)
Fluid overload ^* 1	1/310 (0.32%)	0/306 (0.00%)
Gout ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hyperuricaemia ^* 1	1/310 (0.32%)	0/306 (0.00%)
Hypoalbuminaemia ^* 1	1/310 (0.32%)	0/306 (0.00%)
Hypoglycaemia ^* 1	1/310 (0.32%)	0/306 (0.00%)
Musculoskeletal and connective tissue disorders
Bone pain ^* 1	0/310 (0.00%)	1/306 (0.33%)
Musculoskeletal pain ^* 1	1/310 (0.32%)	0/306 (0.00%)
Osteonecrosis of jaw ^* 1	0/310 (0.00%)	1/306 (0.33%)
Spinal pain ^* 1	0/310 (0.00%)	1/306 (0.33%)
Tendon pain ^* 1	1/310 (0.32%)	0/306 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system ^* 1	0/310 (0.00%)	1/306 (0.33%)
Pancreatic carcinoma ^* 1	0/310 (0.00%)	1/306 (0.33%)
Renal cancer ^* 1	0/310 (0.00%)	1/306 (0.33%)
Tumour necrosis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Nervous system disorders
Ischaemic stroke ^* 1	4/310 (1.29%)	1/306 (0.33%)
Seizure ^* 1	3/310 (0.97%)	2/306 (0.65%)
Transient ischaemic attack ^* 1	1/310 (0.32%)	3/306 (0.98%)
Syncope ^* 1	2/310 (0.65%)	1/306 (0.33%)
Cerebrovascular accident ^* 1	1/310 (0.32%)	1/306 (0.33%)
Haemorrhage intracranial ^* 1	0/310 (0.00%)	2/306 (0.65%)
Cerebellar haemorrhage ^* 1	0/310 (0.00%)	1/306 (0.33%)
Cerebral haemorrhage ^* 1	1/310 (0.32%)	0/306 (0.00%)
Conus medullaris syndrome ^* 1	1/310 (0.32%)	0/306 (0.00%)
Epilepsy ^* 1	1/310 (0.32%)	0/306 (0.00%)
Haemorrhagic stroke ^* 1	0/310 (0.00%)	1/306 (0.33%)
Headache ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hemiplegia ^* 1	1/310 (0.32%)	0/306 (0.00%)
Radiculopathy ^* 1	1/310 (0.32%)	0/306 (0.00%)
Sensory disturbance ^* 1	1/310 (0.32%)	0/306 (0.00%)
Sensory loss ^* 1	1/310 (0.32%)	0/306 (0.00%)
Speech disorder ^* 1	0/310 (0.00%)	1/306 (0.33%)
Spinal cord compression ^* 1	1/310 (0.32%)	0/306 (0.00%)
Psychiatric disorders
Confusional state ^* 1	0/310 (0.00%)	1/306 (0.33%)
Delirium ^* 1	0/310 (0.00%)	1/306 (0.33%)
Renal and urinary disorders
Acute kidney injury ^* 1	4/310 (1.29%)	5/306 (1.63%)
Haematuria ^* 1	0/310 (0.00%)	3/306 (0.98%)
Renal impairment ^* 1	1/310 (0.32%)	2/306 (0.65%)
Anuria ^* 1	2/310 (0.65%)	0/306 (0.00%)
Chronic kidney disease ^* 1	1/310 (0.32%)	0/306 (0.00%)
Lower urinary tract symptoms ^* 1	1/310 (0.32%)	0/306 (0.00%)
Nephrolithiasis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Nephrotic syndrome ^* 1	0/310 (0.00%)	1/306 (0.33%)
Renal failure ^* 1	0/310 (0.00%)	1/306 (0.33%)
Reproductive system and breast disorders
Genital ulceration ^* 1	0/310 (0.00%)	1/306 (0.33%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion ^* 1	7/310 (2.26%)	2/306 (0.65%)
Pulmonary embolism ^* 1	3/310 (0.97%)	4/306 (1.31%)
Dyspnoea ^* 1	2/310 (0.65%)	3/306 (0.98%)
Respiratory failure ^* 1	2/310 (0.65%)	1/306 (0.33%)
Epistaxis ^* 1	0/310 (0.00%)	2/306 (0.65%)
Acute respiratory failure ^* 1	1/310 (0.32%)	0/306 (0.00%)
Aspiration ^* 1	1/310 (0.32%)	0/306 (0.00%)
Haemoptysis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Pneumonia aspiration ^* 1	1/310 (0.32%)	0/306 (0.00%)
Pulmonary mass ^* 1	1/310 (0.32%)	0/306 (0.00%)
Skin and subcutaneous tissue disorders
Decubitus ulcer ^* 1	1/310 (0.32%)	1/306 (0.33%)
Vascular disorders
Hypotension ^* 1	7/310 (2.26%)	0/306 (0.00%)
Deep vein thrombosis ^* 1	3/310 (0.97%)	2/306 (0.65%)
Embolism ^* 1	1/310 (0.32%)	0/306 (0.00%)
Hypertension ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hypertensive crisis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Hypovolaemic shock ^* 1	1/310 (0.32%)	0/306 (0.00%)
Jugular vein thrombosis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Orthostatic hypotension ^* 1	0/310 (0.00%)	1/306 (0.33%)
Pelvic venous thrombosis ^* 1	0/310 (0.00%)	1/306 (0.33%)
Vena cava thrombosis ^* 1	1/310 (0.32%)	0/306 (0.00%)
Venous thrombosis ^* 1	0/310 (0.00%)	1/306 (0.33%)
1 Term from vocabulary, MedDRA (18.1) * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Combination of Bempegaldesleukin + Nivolumab	Sunitinib or Cabozantinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	307/310 (99.03%)	304/306 (99.35%)
Blood and lymphatic system disorders
Anaemia ^* 1	57/310 (18.39%)	109/306 (35.62%)
Neutropenia ^* 1	19/310 (6.13%)	86/306 (28.10%)
Eosinophilia ^* 1	82/310 (26.45%)	3/306 (0.98%)
Thrombocytopenia ^* 1	6/310 (1.94%)	73/306 (23.86%)
Leukopenia ^* 1	3/310 (0.97%)	41/306 (13.40%)
Lymphopenia ^* 1	5/310 (1.61%)	18/306 (5.88%)
Endocrine disorders
Hypothyroidism ^* 1	74/310 (23.87%)	129/306 (42.16%)
Hyperthyroidism ^* 1	45/310 (14.52%)	17/306 (5.56%)
Gastrointestinal disorders
Diarrhoea ^* 1	87/310 (28.06%)	161/306 (52.61%)
Nausea ^* 1	100/310 (32.26%)	119/306 (38.89%)
Vomiting ^* 1	61/310 (19.68%)	74/306 (24.18%)
Abdominal pain ^* 1	32/310 (10.32%)	50/306 (16.34%)
Constipation ^* 1	30/310 (9.68%)	49/306 (16.01%)
Stomatitis ^* 1	9/310 (2.90%)	64/306 (20.92%)
Abdominal pain upper ^* 1	21/310 (6.77%)	34/306 (11.11%)
Dyspepsia ^* 1	14/310 (4.52%)	35/306 (11.44%)
Dry mouth ^* 1	15/310 (4.84%)	17/306 (5.56%)
Gastrooesophageal reflux disease ^* 1	9/310 (2.90%)	16/306 (5.23%)
General disorders
Fatigue ^* 1	72/310 (23.23%)	87/306 (28.43%)
Pyrexia ^* 1	121/310 (39.03%)	28/306 (9.15%)
Asthenia ^* 1	77/310 (24.84%)	57/306 (18.63%)
Oedema peripheral ^* 1	36/310 (11.61%)	39/306 (12.75%)
Chills ^* 1	45/310 (14.52%)	27/306 (8.82%)
Influenza like illness ^* 1	51/310 (16.45%)	8/306 (2.61%)
Mucosal inflammation ^* 1	8/310 (2.58%)	39/306 (12.75%)
Non-cardiac chest pain ^* 1	17/310 (5.48%)	18/306 (5.88%)
Face oedema ^* 1	17/310 (5.48%)	13/306 (4.25%)
Infections and infestations
Corona virus infection ^* 1	36/310 (11.61%)	37/306 (12.09%)
Urinary tract infection ^* 1	14/310 (4.52%)	16/306 (5.23%)
Injury, poisoning and procedural complications
Infusion related reaction ^* 1	18/310 (5.81%)	0/306 (0.00%)
Investigations
Aspartate aminotransferase increased ^* 1	17/310 (5.48%)	71/306 (23.20%)
Alanine aminotransferase increased ^* 1	22/310 (7.10%)	65/306 (21.24%)
Blood creatinine increased ^* 1	48/310 (15.48%)	37/306 (12.09%)
Weight decreased ^* 1	28/310 (9.03%)	56/306 (18.30%)
Lipase increased ^* 1	28/310 (9.03%)	44/306 (14.38%)
Amylase increased ^* 1	14/310 (4.52%)	40/306 (13.07%)
Blood alkaline phosphatase increased ^* 1	15/310 (4.84%)	30/306 (9.80%)
Blood thyroid stimulating hormone increased ^* 1	11/310 (3.55%)	33/306 (10.78%)
Platelet count decreased ^* 1	1/310 (0.32%)	41/306 (13.40%)
Blood creatine phosphokinase increased ^* 1	8/310 (2.58%)	28/306 (9.15%)
Body temperature increased ^* 1	34/310 (10.97%)	1/306 (0.33%)
Blood lactate dehydrogenase increased ^* 1	6/310 (1.94%)	28/306 (9.15%)
Blood pressure increased ^* 1	4/310 (1.29%)	16/306 (5.23%)
Metabolism and nutrition disorders
Decreased appetite ^* 1	82/310 (26.45%)	103/306 (33.66%)
Hyperkalaemia ^* 1	21/310 (6.77%)	22/306 (7.19%)
Hyperglycaemia ^* 1	20/310 (6.45%)	21/306 (6.86%)
Hyponatraemia ^* 1	13/310 (4.19%)	22/306 (7.19%)
Hypocalcaemia ^* 1	5/310 (1.61%)	16/306 (5.23%)
Hypokalaemia ^* 1	4/310 (1.29%)	17/306 (5.56%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	90/310 (29.03%)	76/306 (24.84%)
Back pain ^* 1	53/310 (17.10%)	57/306 (18.63%)
Myalgia ^* 1	70/310 (22.58%)	38/306 (12.42%)
Pain in extremity ^* 1	26/310 (8.39%)	31/306 (10.13%)
Musculoskeletal pain ^* 1	16/310 (5.16%)	16/306 (5.23%)
Nervous system disorders
Headache ^* 1	87/310 (28.06%)	90/306 (29.41%)
Dizziness ^* 1	52/310 (16.77%)	40/306 (13.07%)
Dysgeusia ^* 1	18/310 (5.81%)	65/306 (21.24%)
Hypotonia ^* 1	16/310 (5.16%)	1/306 (0.33%)
Psychiatric disorders
Insomnia ^* 1	34/310 (10.97%)	49/306 (16.01%)
Anxiety ^* 1	26/310 (8.39%)	31/306 (10.13%)
Renal and urinary disorders
Chronic kidney disease ^* 1	15/310 (4.84%)	18/306 (5.88%)
Proteinuria ^* 1	2/310 (0.65%)	31/306 (10.13%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	54/310 (17.42%)	43/306 (14.05%)
Dyspnoea ^* 1	48/310 (15.48%)	24/306 (7.84%)
Dysphonia ^* 1	6/310 (1.94%)	17/306 (5.56%)
Nasal congestion ^* 1	17/310 (5.48%)	2/306 (0.65%)
Skin and subcutaneous tissue disorders
Pruritus ^* 1	105/310 (33.87%)	33/306 (10.78%)
Palmar-plantar erythrodysaesthesia syndrome ^* 1	3/310 (0.97%)	113/306 (36.93%)
Rash ^* 1	74/310 (23.87%)	28/306 (9.15%)
Pruritus generalised ^* 1	53/310 (17.10%)	18/306 (5.88%)
Dry skin ^* 1	24/310 (7.74%)	33/306 (10.78%)
Rash maculo-papular ^* 1	28/310 (9.03%)	13/306 (4.25%)
Erythema ^* 1	24/310 (7.74%)	6/306 (1.96%)
Hair colour changes ^* 1	1/310 (0.32%)	27/306 (8.82%)
Yellow skin ^* 1	0/310 (0.00%)	16/306 (5.23%)
Vascular disorders
Hypertension ^* 1	29/310 (9.35%)	112/306 (36.60%)
Hypotension ^* 1	43/310 (13.87%)	7/306 (2.29%)
1 Term from vocabulary, MedDRA (18.1) * Indicates events were collected by non-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.

Results Point of Contact

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Name/Title:	Study Director
Organization:	Nektar Therapeutics
Phone:	4154825300
EMail:	StudyInquiry@nektar.com

Layout table for additonal information

Responsible Party:	Nektar Therapeutics
ClinicalTrials.gov Identifier:	NCT03729245
Other Study ID Numbers:	17-214-09 CA045002 ( Other Identifier: Bristol-Myers Squibb Protocol ID )
First Submitted:	October 29, 2018
First Posted:	November 2, 2018
Results First Submitted:	February 17, 2023
Results First Posted:	April 11, 2023
Last Update Posted:	April 11, 2023

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