A Dose Escalation and Cohort Expansion Study of NKTR-214 in Combination With Nivolumab and Other Anti-Cancer Therapies in Patients With Select Advanced Solid Tumors (PIVOT-02)

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ClinicalTrials.gov Identifier: NCT02983045

Recruitment Status : Completed

First Posted : December 6, 2016

Results First Posted : March 13, 2023

Last Update Posted : March 13, 2023

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Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by (Responsible Party):

Nektar Therapeutics

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Melanoma Renal Cell Carcinoma Non Small Cell Lung Cancer Urothelial Carcinoma Triple Negative Breast Cancer HR+/HER2- Breast Cancer Gastric Cancer
Interventions	Drug: Dose Escalation Doublet: Combination of NKTR-214 + nivolumab Drug: Dose Expansion Doublet: Combination of NKTR-214 + nivolumab Drug: Schedule Finding Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab Drug: Dose Expansion Triplet: Combination of NKTR-214+ nivolumab+ ipilimumab
Enrollment	557

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
Arm/Group Description	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	In this Part 2 of the study, the pa...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	Experimental Combination of NKTR-21...
Arm/Group Description	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.003 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.009 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	In this Part 2 of the study, the patients will receive a combination of NKTR-214 + nivolumab at the RP2D (NKTR 214 0.006 mg/kg q3w + nivolumab 360 mg q3w) with or without chemotherapy.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 1, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 360 mg flat dose q3w + ipilimumab at 1 mg/kg q6w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 2, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 1 mg/kg q3w + ipilimumab at 3 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 3, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 3 mg/kg q3w + ipilimumab at 1 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	Experimental Combination of NKTR-214 + nivolumab + ipilimumab Combination of NKTR-214 + nivolumab: Combination of NKTR-214 + nivolumab +ipilimumab administered at the RP2D dose/schedule.
Period Title: Overall Study
Started	4	3	3	25	3	476	10	8	6	19
Completed	4	2	3	20	3	394	10	8	6	17
Not Completed	0	1	0	5	0	82	0	0	0	2
Reason Not Completed
Withdrawal by Subject	0	1	0	5	0	72	0	0	0	2
Lost to Follow-up	0	0	0	0	0	10	0	0	0	0

Baseline Characteristics

Arm/Group Title		Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab	Total
Arm/Group Description		NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	In this Part 2 of the study, the pa...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	Experimental Combination of NKTR-21...	Total of all reporting groups
Arm/Group Description		NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.003 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.009 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	In this Part 2 of the study, the patients will receive a combination of NKTR-214 + nivolumab at the RP2D (NKTR 214 0.006 mg/kg q3w + nivolumab 360 mg q3w) with or without chemotherapy.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 1, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 360 mg flat dose q3w + ipilimumab at 1 mg/kg q6w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 2, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 1 mg/kg q3w + ipilimumab at 3 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 3, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 3 mg/kg q3w + ipilimumab at 1 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	Experimental Combination of NKTR-214 + nivolumab ipilimumab that may enroll between 12-26 patients per tumor type Combination of NKTR-214 + nivolumab: Combination of NKTR-214 + nivolumab +ipilimumab administered at the RP2D dose/schedule.	Total of all reporting groups
Overall Number of Baseline Participants		4	3	3	25	3	476	10	8	6	19	557
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	4 participants	3 participants	3 participants	25 participants	3 participants	476 participants	10 participants	8 participants	6 participants	19 participants	557 participants
		54.8 (10.90)	61.7 (7.37)	57.0 (7.81)	59.2 (10.12)	55.7 (6.81)	62.1 (11.48)	62.4 (9.45)	64.3 (5.85)	61.2 (9.3)	59.1 (12.63)	61.7 (11.32)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	3 participants	25 participants	3 participants	476 participants	10 participants	8 participants	6 participants	19 participants	557 participants
	Female	2 50.0%	0 0.0%	0 0.0%	5 20.0%	1 33.3%	207 43.5%	1 10.0%	0 0.0%	0 0.0%	5 26.3%	221 39.7%
	Male	2 50.0%	3 100.0%	3 100.0%	20 80.0%	2 66.7%	269 56.5%	9 90.0%	8 100.0%	6 100.0%	14 73.7%	336 60.3%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	3 participants	25 participants	3 participants	476 participants	10 participants	8 participants	6 participants	19 participants	557 participants
	Hispanic or Latino	0 0.0%	0 0.0%	2 66.7%	0 0.0%	2 66.7%	35 7.4%	1 10.0%	2 25.0%	2 33.3%	2 10.5%	46 8.3%
	Not Hispanic or Latino	4 100.0%	3 100.0%	1 33.3%	24 96.0%	1 33.3%	413 86.8%	9 90.0%	6 75.0%	4 66.7%	15 78.9%	480 86.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	1 4.0%	0 0.0%	28 5.9%	0 0.0%	0 0.0%	0 0.0%	2 10.5%	31 5.6%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	3 participants	3 participants	25 participants	3 participants	476 participants	10 participants	8 participants	6 participants	19 participants	557 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 0.4%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 0.4%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	13 2.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	13 2.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	2 8.0%	0 0.0%	16 3.4%	1 10.0%	1 12.5%	0 0.0%	0 0.0%	20 3.6%
	White	4 100.0%	3 100.0%	3 100.0%	23 92.0%	3 100.0%	413 86.8%	8 80.0%	7 87.5%	5 83.3%	17 89.5%	486 87.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.2%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	31 6.5%	1 10.0%	0 0.0%	1 16.7%	2 10.5%	35 6.3%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	4 participants	3 participants	3 participants	25 participants	3 participants	476 participants	10 participants	8 participants	6 participants	19 participants	557 participants
Canada		0	0	0	0	0	27	0	0	0	0	27
Belgium		0	0	0	0	0	29	0	0	0	0	29
United States		4	3	3	25	3	295	10	8	6	19	376
Poland		0	0	0	0	0	23	0	0	0	0	23
Italy		0	0	0	0	0	35	0	0	0	0	35
United Kingdom		0	0	0	0	0	6	0	0	0	0	6
France		0	0	0	0	0	14	0	0	0	0	14
Spain		0	0	0	0	0	47	0	0	0	0	47
ECOG Performance Status ^[1] Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	4 participants	3 participants	3 participants	25 participants	3 participants	476 participants	10 participants	8 participants	6 participants	19 participants	557 participants
0		3 75.0%	2 66.7%	2 66.7%	16 64.0%	3 100.0%	221 46.4%	6 60.0%	6 75.0%	5 83.3%	12 63.2%	276 49.6%
1		1 25.0%	1 33.3%	1 33.3%	9 36.0%	0 0.0%	254 53.4%	4 40.0%	2 25.0%	1 16.7%	7 36.8%	280 50.3%
Data Missing		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.2%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.2%
		[1] Measure Description: Eastern Cooperative Oncology Group (ECOG) performance status: ECOG Performance Status of 0 = Able to carry out all normal activities without restriction ECOG Performance Status of 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature

Outcome Measures

1.Primary Outcome


Title	Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window
Description	Part 1of the study was a dose-escalation phase that evaluated the safe...
Description	Part 1of the study was a dose-escalation phase that evaluated the safety and tolerability and defined the maximum tolerated dose or recommended Phase 2 dose of the NKTR-214/nivolumab doublet across 5 dosage/schedule levels. The results presented are for the DLT Population.
Time Frame	Includes DLTs that occurred within the DLT window of at least 21 days after the first dose of study treatment (28 days for every 2 weeks dosing; 21 days for every 3 weeks dosing). Patients were counted only once under each preferred term.

Outcome Measure Data

Analysis Population Description

The DLT population included all Part 1 patients who took study treatment and followed up at least through the DLT evaluation period (q2w dosing: received ≥ 2 cycles of study treatment and stayed in study for at least 28 days; q3w dosing: received at least 1 cycle of study treatment and stayed in study for at least 21 days) or discontinued from study treatment due to DLT.


Arm/Group Title	Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w
Arm/Group Description:	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...
Arm/Group Description:	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.003 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.009 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.
Overall Number of Participants Analyzed	4	3	3	24	3
Measure Type: Count of Participants Unit of Measure: Participants
At least 1 DLT	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 66.7%
Metabolism and Nutrition Disorders: Acidosis	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%
Metabolism and Nutrition Disorders: Hyperglycaemia	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%
Vascular Disorders: Hypotension	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%

2.Primary Outcome


Title	Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window
Description	Part 3 of the study was a schedule finding phase to establish the reco...
Description	Part 3 of the study was a schedule finding phase to establish the recommended phase 2 dosing schedules for Part 4 and assess the safety and tolerability for the NKTR-214/nivolumab/ipilimumab triplet combination. The results presented are for the DLT Population.
Time Frame	Dose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.

Outcome Measure Data

Analysis Population Description

The DLT population included all Part 3 patients who received at least 1 cycle of study treatment and stayed in study for at least 21 days after first dose of ipilimumab or discontinued from study treatment due to DLT.


Arm/Group Title	Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab
Arm/Group Description:	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...
Arm/Group Description:	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 1, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 360 mg flat dose q3w + ipilimumab at 1 mg/kg q6w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 2, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 1 mg/kg q3w + ipilimumab at 3 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 3, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 3 mg/kg q3w + ipilimumab at 1 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.
Overall Number of Participants Analyzed	10	8	6
Measure Type: Count of Participants Unit of Measure: Participants
Patients with at least one event	1 10.0%	1 12.5%	1 16.7%
Endocrine disorders: Adrenal insufficiency	0 0.0%	1 12.5%	0 0.0%
Endocrine disorders: Hyperthyroidism	0 0.0%	0 0.0%	1 16.7%
Metabolism and nutrition disorders: Hyponatraemia	1 10.0%	0 0.0%	0 0.0%

3.Primary Outcome


Title	Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)
Description	Objective Response Rate (ORR) per Response Evaluation Criteria in Soli...
Description	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) at Recommended Phase 2 Dose (RP2D). ORR is defined as the percentage 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	Tumor assessment at Screening then every 8 weeks (± 7 days) from Cycle 1 Day 1 and end of treatment (unless scan done within 4 weeks) up to approximately 27 months.

Outcome Measure Data

Analysis Population Description

The response evaluable population included patients who had measurable disease (per RECIST 1.1) at baseline and also had at least 1 postbaseline assessment of tumor response prior to receiving new systemic anticancer therapy, surgical procedures or radiotherapy on target lesions.


Arm/Group Title	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
Arm/Group Description:	In this Part 2 of the study, the pa...	Experimental Combination of NKTR-21...
Arm/Group Description:	In this Part 2 of the study, the patients received a combination of NKTR-214 + nivolumab at the RP2D (NKTR 214 0.006 mg/kg q3w + nivolumab 360 mg q3w) with or without chemotherapy.	Experimental Combination of NKTR-214 + nivolumab + ipilimumab Combination of NKTR-214 + nivolumab: Combination of NKTR-214 + nivolumab +ipilimumab administered at the RP2D dose/schedule.
Overall Number of Participants Analyzed	429	17
Measure Type: Count of Participants Unit of Measure: Participants
	64 14.9%	3 17.6%

Adverse Events

Time Frame	AEs were reported from the time of first study drug(s) administration until 100 days after the last dose of all study drug(s), up to a maximum of approximately 2.5 years.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
Arm/Group Description	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	NKTR-214 in escalating doses combin...	In this Part 2 of the study, the pa...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	In this Part 3 of the study, patien...	Experimental Combination of NKTR-21...
Arm/Group Description	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.003 mg/kg administered every 2 weeks (q2w) in combination with 240 mg nivolumab q2w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.006 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	NKTR-214 in escalating doses combined with one of the two proposed doses of nivolumab. The goal of this dose escalation Part 1 of the study is to find the RP2D. Patients will receive NKTR-214 at 0.009 mg/kg administered every 3 weeks (q3w) in combination with 360 mg nivolumab q3w.	In this Part 2 of the study, the patients will receive a combination of NKTR-214 + nivolumab at the RP2D (NKTR 214 0.006 mg/kg q3w + nivolumab 360 mg q3w) with or without chemotherapy.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 1, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 360 mg flat dose q3w + ipilimumab at 1 mg/kg q6w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 2, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 1 mg/kg q3w + ipilimumab at 3 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	In this Part 3 of the study, patients will receive a combination of NKTR-214 at 0.006 mg/kg q3w with nivolumab and ipilimumab in up to three different dosing schedules to identify dose and schedules that proceed into Part 4. In Schedule 3, patients received NKTR-214 at 0.006 mg/kg q3w + nivolumab at 3 mg/kg q3w + ipilimumab at 1 mg/kg q3w for four cycles, followed by the maintenance dose of NKTR-214 0.006 mg/kg and nivolumab 360 mg q3w.	Experimental Combination of NKTR-214 + nivolumab + ipilimumab. Combination of NKTR-214 + nivolumab: Combination of NKTR-214 + nivolumab +ipilimumab administered at the RP2D dose/schedule.
All-Cause Mortality
	Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/4 (50.00%)	1/3 (33.33%)	2/3 (66.67%)	10/25 (40.00%)	1/3 (33.33%)	291/476 (61.13%)	2/10 (20.00%)	3/8 (37.50%)	1/6 (16.67%)	5/19 (26.32%)
Serious Adverse Events Serious Adverse Events
	Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/4 (50.00%)	0/3 (0.00%)	1/3 (33.33%)	9/25 (36.00%)	2/3 (66.67%)	213/476 (44.75%)	6/10 (60.00%)	5/8 (62.50%)	2/6 (33.33%)	8/19 (42.11%)
Blood and lymphatic system disorders
Anaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Eosinophilia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypereosinophilic syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Microcytic anaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cardiac disorders
Atrial fibrillation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	11/476 (2.31%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Pericardial effusion ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cardiac arrest ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Myocarditis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Acute coronary syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Acute myocardial infarction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Angina pectoris ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Arrhythmia supraventricular ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Atrial flutter ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cardiac failure acute ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cardio-respiratory arrest ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Myocardial infarction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pericarditis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Supraventricular tachycardia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Ventricular tachycardia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Endocrine disorders
Adrenal insufficiency ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Hyperthyroidism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Autoimmune hypothyroidism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypophysitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Hypothyroidism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Thyroiditis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Eye disorders
Visual impairment ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Gastrointestinal disorders
Nausea ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vomiting ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Diarrhoea ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Abdominal pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pancreatitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Colitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Diverticulum intestinal haemorrhagic ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dysphagia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Enterocolitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Faecaloma ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Gastrointestinal haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Gastrooesophageal reflux disease ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Haematemesis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Large intestinal obstruction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Large intestine perforation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Oesophageal stenosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Rectal haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Small intestinal obstruction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Upper gastrointestinal haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
General disorders
Pyrexia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	16/476 (3.36%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Fatigue ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Malaise ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Non-cardiac chest pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Asthenia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Chills ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Face oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
General physical health deterioration ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Influenza like illness ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Oedema peripheral ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hepatobiliary disorders
Autoimmune hepatitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hepatic function abnormal ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Immune system disorders
Cytokine release syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Contrast media allergy ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Infections and infestations
Pneumonia ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	11/476 (2.31%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Urinary tract infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Sepsis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Cellulitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Bronchitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Corona virus infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Infectious pleural effusion ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Lower respiratory tract infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Respiratory tract infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Abscess soft tissue ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Bronchopulmonary aspergillosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Bursitis infective staphylococcal ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Device related infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Device related sepsis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Gastroenteritis ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Herpes zoster ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Lower respiratory tract infection viral ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Lung infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Systemic infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Urosepsis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Injury, poisoning and procedural complications
Infusion related reaction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Fall ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Subdural haematoma ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Craniocerebral injury ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Multiple fractures ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Investigations
Blood creatinine increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Alanine aminotransferase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Aspartate aminotransferase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Neutrophil count decreased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Metabolism and nutrition disorders
Hyponatraemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	7/476 (1.47%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dehydration ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	7/476 (1.47%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypercalcaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hyperglycaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Acidosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Failure to thrive ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hyperkalaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Flank pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pain in extremity ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Arthralgia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Groin pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Musculoskeletal chest pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Myalgia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Myositis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pain in jaw ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pathological fracture ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Rhabdomyolysis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Spinal pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Tumour haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Bladder cancer ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Intracranial tumour haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Metastases to central nervous system ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Oesophageal squamous cell carcinoma ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Squamous cell carcinoma ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Nervous system disorders
Cerebrovascular accident ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	1/19 (5.26%)
Embolic stroke ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Headache ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dizziness ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Brain oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cerebral infarction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Encephalopathy ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Facial paralysis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hydrocephalus ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Myasthenia gravis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Seizure ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Somnolence ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Spinal cord compression ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Syncope ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vasogenic cerebral oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Psychiatric disorders
Confusional state ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hallucination ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Insomnia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Mental status changes ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Renal and urinary disorders
Acute kidney injury ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	7/476 (1.47%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Autoimmune nephritis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Haematuria ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hydronephrosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Nephrolithiasis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Obstructive uropathy ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Reproductive system and breast disorders
Pelvic pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	14/476 (2.94%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Pleural effusion ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pneumonitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pulmonary embolism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Chronic obstructive pulmonary disease ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Respiratory failure ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Haemoptysis ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypoxia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pneumothorax ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pulmonary oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Acute respiratory failure ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Bronchial obstruction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Bronchospasm ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cough ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Diaphragmatic spasm ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Laryngeal inflammation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pulmonary haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Rash erythematous ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Angioedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Erythema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pemphigoid ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vascular disorders
Hypotension ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	15/476 (3.15%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Embolism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Superior vena cava syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypertension ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Deep vein thrombosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vena cava thrombosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Venous thrombosis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
1 Term from vocabulary, MedDRA 19.0 * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part 1 Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w	Part 1 Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 1 Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 2 Dose Expansion: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w	Part 3 Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab	Part 3 Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab	Part 4 Dose Expansion of NKTR-214 + Nivolumab + Ipilimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/4 (100.00%)	3/3 (100.00%)	3/3 (100.00%)	25/25 (100.00%)	3/3 (100.00%)	468/476 (98.32%)	10/10 (100.00%)	8/8 (100.00%)	6/6 (100.00%)	19/19 (100.00%)
Blood and lymphatic system disorders
Anaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	51/476 (10.71%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	4/19 (21.05%)
Eosinophilia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	9/476 (1.89%)	1/10 (10.00%)	0/8 (0.00%)	2/6 (33.33%)	0/19 (0.00%)
Haemorrhagic anaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Heparin-induced thrombocytopenia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Cardiac disorders
Sinus tachycardia ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/25 (8.00%)	0/3 (0.00%)	11/476 (2.31%)	1/10 (10.00%)	1/8 (12.50%)	1/6 (16.67%)	5/19 (26.32%)
Tachycardia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	17/476 (3.57%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Palpitations ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	10/476 (2.10%)	2/10 (20.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Atrial fibrillation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	9/476 (1.89%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Angina pectoris ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Atrial flutter ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Myocardial infarction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Pericardial effusion ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Stress cardiomyopathy ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Ear and labyrinth disorders
Ear pain ^* 1	1/4 (25.00%)	1/3 (33.33%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	9/476 (1.89%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vertigo ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Tinnitus ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Endocrine disorders
Hypothyroidism ^* 1	2/4 (50.00%)	0/3 (0.00%)	0/3 (0.00%)	7/25 (28.00%)	1/3 (33.33%)	65/476 (13.66%)	2/10 (20.00%)	5/8 (62.50%)	2/6 (33.33%)	5/19 (26.32%)
Hyperthyroidism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	25/476 (5.25%)	0/10 (0.00%)	3/8 (37.50%)	1/6 (16.67%)	2/19 (10.53%)
Thyroiditis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	4/476 (0.84%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Hypogonadism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Adrenal insufficiency ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Hypophysitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Eye disorders
Dry eye ^* 1	0/4 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/25 (4.00%)	0/3 (0.00%)	12/476 (2.52%)	2/10 (20.00%)	1/8 (12.50%)	0/6 (0.00%)	4/19 (21.05%)
Vision blurred ^* 1	1/4 (25.00%)	1/3 (33.33%)	0/3 (0.00%)	4/25 (16.00%)	0/3 (0.00%)	12/476 (2.52%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Periorbital oedema ^* 1	1/4 (25.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	9/476 (1.89%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Eye swelling ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	9/476 (1.89%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Lacrimation increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	2/25 (8.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Eyelid oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Photophobia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Eye pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/25 (4.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Ocular hyperaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Eye irritation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Vitreous floaters ^* 1	0/4 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Orbital oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Chalazion ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Gastrointestinal disorders
Nausea ^* 1	3/4 (75.00%)	1/3 (33.33%)	1/3 (33.33%)	13/25 (52.00%)	1/3 (33.33%)	191/476 (40.13%)	8/10 (80.00%)	4/8 (50.00%)	6/6 (100.00%)	11/19 (57.89%)
Diarrhoea ^* 1	3/4 (75.00%)	2/3 (66.67%)	2/3 (66.67%)	13/25 (52.00%)	2/3 (66.67%)	126/476 (26.47%)	8/10 (80.00%)	6/8 (75.00%)	2/6 (33.33%)	10/19 (52.63%)
Vomiting ^* 1	2/4 (50.00%)	1/3 (33.33%)	1/3 (33.33%)	7/25 (28.00%)	2/3 (66.67%)	117/476 (24.58%)	5/10 (50.00%)	3/8 (37.50%)	5/6 (83.33%)	5/19 (26.32%)
Constipation ^* 1	2/4 (50.00%)	1/3 (33.33%)	1/3 (33.33%)	8/25 (32.00%)	1/3 (33.33%)	98/476 (20.59%)	4/10 (40.00%)	3/8 (37.50%)	3/6 (50.00%)	2/19 (10.53%)
Dry mouth ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	4/25 (16.00%)	1/3 (33.33%)	57/476 (11.97%)	3/10 (30.00%)	1/8 (12.50%)	2/6 (33.33%)	2/19 (10.53%)
Abdominal pain ^* 1	1/4 (25.00%)	1/3 (33.33%)	1/3 (33.33%)	8/25 (32.00%)	1/3 (33.33%)	50/476 (10.50%)	1/10 (10.00%)	2/8 (25.00%)	2/6 (33.33%)	0/19 (0.00%)
Dyspepsia ^* 1	1/4 (25.00%)	0/3 (0.00%)	1/3 (33.33%)	4/25 (16.00%)	1/3 (33.33%)	35/476 (7.35%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Stomatitis ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	1/3 (33.33%)	29/476 (6.09%)	1/10 (10.00%)	2/8 (25.00%)	1/6 (16.67%)	2/19 (10.53%)
Abdominal pain upper ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	21/476 (4.41%)	0/10 (0.00%)	2/8 (25.00%)	1/6 (16.67%)	1/19 (5.26%)
Abdominal distension ^* 1	1/4 (25.00%)	1/3 (33.33%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	16/476 (3.36%)	0/10 (0.00%)	0/8 (0.00%)	2/6 (33.33%)	0/19 (0.00%)
Gastrooesophageal reflux disease ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	14/476 (2.94%)	2/10 (20.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dysphagia ^* 1	0/4 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/25 (4.00%)	0/3 (0.00%)	13/476 (2.73%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Swollen tongue ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	1/3 (33.33%)	10/476 (2.10%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Flatulence ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	7/476 (1.47%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Haemorrhoids ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Tongue oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Ascites ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Abdominal pain lower ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Colitis ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	1/476 (0.21%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Anal haemorrhage ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypoaesthesia oral ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Oral disorder ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Oral dysaesthesia ^* 1	2/4 (50.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Toothache ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Retching ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Abdominal rigidity ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Anal fistula ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Frequent bowel movements ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Lip oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Salivary gland pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
General disorders
Fatigue ^* 1	4/4 (100.00%)	2/3 (66.67%)	1/3 (33.33%)	19/25 (76.00%)	2/3 (66.67%)	241/476 (50.63%)	9/10 (90.00%)	5/8 (62.50%)	6/6 (100.00%)	15/19 (78.95%)
Pyrexia ^* 1	4/4 (100.00%)	3/3 (100.00%)	2/3 (66.67%)	13/25 (52.00%)	3/3 (100.00%)	228/476 (47.90%)	7/10 (70.00%)	3/8 (37.50%)	5/6 (83.33%)	10/19 (52.63%)
Influenza like illness ^* 1	3/4 (75.00%)	0/3 (0.00%)	0/3 (0.00%)	14/25 (56.00%)	1/3 (33.33%)	126/476 (26.47%)	6/10 (60.00%)	6/8 (75.00%)	6/6 (100.00%)	13/19 (68.42%)
Chills ^* 1	3/4 (75.00%)	3/3 (100.00%)	3/3 (100.00%)	16/25 (64.00%)	2/3 (66.67%)	115/476 (24.16%)	5/10 (50.00%)	3/8 (37.50%)	1/6 (16.67%)	7/19 (36.84%)
Oedema peripheral ^* 1	1/4 (25.00%)	2/3 (66.67%)	1/3 (33.33%)	11/25 (44.00%)	2/3 (66.67%)	90/476 (18.91%)	3/10 (30.00%)	3/8 (37.50%)	4/6 (66.67%)	5/19 (26.32%)
Asthenia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	1/3 (33.33%)	70/476 (14.71%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Face oedema ^* 1	2/4 (50.00%)	0/3 (0.00%)	1/3 (33.33%)	5/25 (20.00%)	1/3 (33.33%)	27/476 (5.67%)	2/10 (20.00%)	2/8 (25.00%)	1/6 (16.67%)	2/19 (10.53%)
Malaise ^* 1	2/4 (50.00%)	0/3 (0.00%)	1/3 (33.33%)	3/25 (12.00%)	0/3 (0.00%)	24/476 (5.04%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Non-cardiac chest pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	4/25 (16.00%)	0/3 (0.00%)	23/476 (4.83%)	1/10 (10.00%)	1/8 (12.50%)	2/6 (33.33%)	0/19 (0.00%)
Pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	20/476 (4.20%)	1/10 (10.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Peripheral swelling ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	17/476 (3.57%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Mucosal inflammation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	1/3 (33.33%)	16/476 (3.36%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Localised oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	12/476 (2.52%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	8/476 (1.68%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Generalised oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	2/19 (10.53%)
Gait disturbance ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Axillary pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hernia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Hypothermia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Immune system disorders
Hypersensitivity ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/25 (4.00%)	0/3 (0.00%)	8/476 (1.68%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Contrast media allergy ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/25 (4.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	2/19 (10.53%)
Infections and infestations
Urinary tract infection ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	35/476 (7.35%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Upper respiratory tract infection ^* 1	1/4 (25.00%)	1/3 (33.33%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	28/476 (5.88%)	3/10 (30.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Sinusitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	7/476 (1.47%)	0/10 (0.00%)	2/8 (25.00%)	1/6 (16.67%)	0/19 (0.00%)
Conjunctivitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pneumonia ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Bronchitis ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Influenza ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Skin infection ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	3/476 (0.63%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Herpes zoster ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Eye infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Gastroenteritis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Mucosal infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Wound infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Gastroenteritis pseudomonas ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Groin infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Pneumonia streptococcal ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Post procedural cellulitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Soft tissue infection ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Injury, poisoning and procedural complications
Infusion related reaction ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	29/476 (6.09%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	2/19 (10.53%)
Procedural pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Contusion ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Sunburn ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Ankle fracture ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Gastrointestinal stoma complication ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Investigations
Weight decreased ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	3/25 (12.00%)	1/3 (33.33%)	64/476 (13.45%)	2/10 (20.00%)	1/8 (12.50%)	1/6 (16.67%)	3/19 (15.79%)
Blood creatinine increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	30/476 (6.30%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Weight increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	1/3 (33.33%)	18/476 (3.78%)	2/10 (20.00%)	1/8 (12.50%)	1/6 (16.67%)	1/19 (5.26%)
Alanine aminotransferase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	16/476 (3.36%)	1/10 (10.00%)	0/8 (0.00%)	2/6 (33.33%)	1/19 (5.26%)
Lipase increased ^* 1	0/4 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	1/25 (4.00%)	0/3 (0.00%)	13/476 (2.73%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Aspartate aminotransferase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	13/476 (2.73%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	1/19 (5.26%)
Amylase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	10/476 (2.10%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Gamma-glutamyltransferase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	1/19 (5.26%)
Blood alkaline phosphatase increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Transaminases increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Eosinophil count increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Blood pressure increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
White blood cell count increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	2/10 (20.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Troponin I increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Blood creatine increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Metabolism and nutrition disorders
Decreased appetite ^* 1	3/4 (75.00%)	2/3 (66.67%)	0/3 (0.00%)	12/25 (48.00%)	2/3 (66.67%)	168/476 (35.29%)	4/10 (40.00%)	4/8 (50.00%)	6/6 (100.00%)	9/19 (47.37%)
Dehydration ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	41/476 (8.61%)	2/10 (20.00%)	2/8 (25.00%)	2/6 (33.33%)	1/19 (5.26%)
Hypokalaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	23/476 (4.83%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hyponatraemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	19/476 (3.99%)	1/10 (10.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Hypomagnesaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	17/476 (3.57%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Hyperkalaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	8/476 (1.68%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Hyperglycaemia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	1/3 (33.33%)	7/476 (1.47%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Fluid retention ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Failure to thrive ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	4/4 (100.00%)	1/3 (33.33%)	2/3 (66.67%)	14/25 (56.00%)	1/3 (33.33%)	114/476 (23.95%)	2/10 (20.00%)	2/8 (25.00%)	5/6 (83.33%)	6/19 (31.58%)
Myalgia ^* 1	3/4 (75.00%)	0/3 (0.00%)	0/3 (0.00%)	9/25 (36.00%)	0/3 (0.00%)	80/476 (16.81%)	2/10 (20.00%)	1/8 (12.50%)	1/6 (16.67%)	2/19 (10.53%)
Back pain ^* 1	2/4 (50.00%)	2/3 (66.67%)	0/3 (0.00%)	9/25 (36.00%)	0/3 (0.00%)	68/476 (14.29%)	2/10 (20.00%)	0/8 (0.00%)	4/6 (66.67%)	2/19 (10.53%)
Pain in extremity ^* 1	0/4 (0.00%)	2/3 (66.67%)	1/3 (33.33%)	5/25 (20.00%)	0/3 (0.00%)	45/476 (9.45%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	2/19 (10.53%)
Musculoskeletal pain ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	2/3 (66.67%)	30/476 (6.30%)	3/10 (30.00%)	1/8 (12.50%)	1/6 (16.67%)	2/19 (10.53%)
Muscular weakness ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	28/476 (5.88%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	2/19 (10.53%)
Neck pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	4/25 (16.00%)	0/3 (0.00%)	19/476 (3.99%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	2/19 (10.53%)
Musculoskeletal chest pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	6/25 (24.00%)	0/3 (0.00%)	17/476 (3.57%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Flank pain ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/25 (4.00%)	1/3 (33.33%)	14/476 (2.94%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Muscle spasms ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	11/476 (2.31%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Musculoskeletal stiffness ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	12/476 (2.52%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Pain in jaw ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	9/476 (1.89%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Arthritis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Bone pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	9/476 (1.89%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Groin pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Joint stiffness ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Bursitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Rotator cuff syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Joint range of motion decreased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Osteoarthritis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Plantar fasciitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Soft tissue swelling ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Cancer pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Skin neoplasm bleeding ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Nervous system disorders
Headache ^* 1	4/4 (100.00%)	1/3 (33.33%)	1/3 (33.33%)	12/25 (48.00%)	1/3 (33.33%)	73/476 (15.34%)	2/10 (20.00%)	2/8 (25.00%)	3/6 (50.00%)	6/19 (31.58%)
Dizziness ^* 1	1/4 (25.00%)	0/3 (0.00%)	1/3 (33.33%)	7/25 (28.00%)	1/3 (33.33%)	79/476 (16.60%)	2/10 (20.00%)	3/8 (37.50%)	3/6 (50.00%)	5/19 (26.32%)
Dysgeusia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	5/25 (20.00%)	1/3 (33.33%)	32/476 (6.72%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	2/19 (10.53%)
Paraesthesia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	28/476 (5.88%)	0/10 (0.00%)	3/8 (37.50%)	2/6 (33.33%)	1/19 (5.26%)
Syncope ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	18/476 (3.78%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Peripheral sensory neuropathy ^* 1	2/4 (50.00%)	1/3 (33.33%)	0/3 (0.00%)	6/25 (24.00%)	1/3 (33.33%)	7/476 (1.47%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Neuropathy peripheral ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	13/476 (2.73%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Memory impairment ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	7/476 (1.47%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Presyncope ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	1/3 (33.33%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Sciatica ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Somnolence ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Tremor ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dizziness postural ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	2/19 (10.53%)
Aphasia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Dysaesthesia ^* 1	1/4 (25.00%)	1/3 (33.33%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Sinus headache ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Carpal tunnel syndrome ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Akathisia ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Balint's syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Facial paralysis ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hemianopia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vasogenic cerebral oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Visual field defect ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Psychiatric disorders
Insomnia ^* 1	0/4 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	5/25 (20.00%)	1/3 (33.33%)	51/476 (10.71%)	3/10 (30.00%)	1/8 (12.50%)	3/6 (50.00%)	5/19 (26.32%)
Confusional state ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	16/476 (3.36%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	1/19 (5.26%)
Anxiety ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	14/476 (2.94%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Restlessness ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Claustrophobia ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Suicidal ideation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Renal and urinary disorders
Dysuria ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	13/476 (2.73%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Haematuria ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	11/476 (2.31%)	1/10 (10.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Acute kidney injury ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	7/476 (1.47%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	1/19 (5.26%)
Pollakiuria ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	7/476 (1.47%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Renal failure ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	2/19 (10.53%)
Urinary retention ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Nocturia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	3/19 (15.79%)
Micturition urgency ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	1/19 (5.26%)
Urinary incontinence ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Chromaturia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Proteinuria ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Bladder spasm ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Nephritis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Nephrotic syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Urine odour abnormal ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Reproductive system and breast disorders
Testicular pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Perineal pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	1/4 (25.00%)	1/3 (33.33%)	1/3 (33.33%)	15/25 (60.00%)	2/3 (66.67%)	118/476 (24.79%)	4/10 (40.00%)	4/8 (50.00%)	2/6 (33.33%)	7/19 (36.84%)
Dyspnoea ^* 1	2/4 (50.00%)	0/3 (0.00%)	0/3 (0.00%)	5/25 (20.00%)	0/3 (0.00%)	94/476 (19.75%)	5/10 (50.00%)	4/8 (50.00%)	1/6 (16.67%)	6/19 (31.58%)
Nasal congestion ^* 1	2/4 (50.00%)	1/3 (33.33%)	3/3 (100.00%)	10/25 (40.00%)	2/3 (66.67%)	49/476 (10.29%)	2/10 (20.00%)	4/8 (50.00%)	4/6 (66.67%)	3/19 (15.79%)
Oropharyngeal pain ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	5/25 (20.00%)	2/3 (66.67%)	34/476 (7.14%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	2/19 (10.53%)
Dysphonia ^* 1	2/4 (50.00%)	0/3 (0.00%)	0/3 (0.00%)	5/25 (20.00%)	0/3 (0.00%)	24/476 (5.04%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Productive cough ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	5/25 (20.00%)	0/3 (0.00%)	20/476 (4.20%)	2/10 (20.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Wheezing ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	19/476 (3.99%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Upper-airway cough syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	19/476 (3.99%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Rhinitis allergic ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	16/476 (3.36%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	2/19 (10.53%)
Rhinorrhoea ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	18/476 (3.78%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dyspnoea exertional ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	18/476 (3.78%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Hypoxia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	10/476 (2.10%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Haemoptysis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	10/476 (2.10%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pharyngeal oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Hiccups ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	5/476 (1.05%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Pneumonitis ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pulmonary embolism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	0/19 (0.00%)
Sinus congestion ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Sneezing ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Pulmonary oedema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Sputum increased ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Upper airway obstruction ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Aspiration ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Hyperventilation ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pulmonary pain ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Throat tightness ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus ^* 1	2/4 (50.00%)	2/3 (66.67%)	2/3 (66.67%)	14/25 (56.00%)	2/3 (66.67%)	181/476 (38.03%)	4/10 (40.00%)	6/8 (75.00%)	6/6 (100.00%)	9/19 (47.37%)
Rash ^* 1	3/4 (75.00%)	1/3 (33.33%)	2/3 (66.67%)	14/25 (56.00%)	3/3 (100.00%)	123/476 (25.84%)	5/10 (50.00%)	1/8 (12.50%)	1/6 (16.67%)	1/19 (5.26%)
Rash maculo-papular ^* 1	1/4 (25.00%)	0/3 (0.00%)	1/3 (33.33%)	5/25 (20.00%)	0/3 (0.00%)	73/476 (15.34%)	5/10 (50.00%)	4/8 (50.00%)	4/6 (66.67%)	11/19 (57.89%)
Dry skin ^* 1	1/4 (25.00%)	2/3 (66.67%)	1/3 (33.33%)	8/25 (32.00%)	2/3 (66.67%)	63/476 (13.24%)	1/10 (10.00%)	2/8 (25.00%)	5/6 (83.33%)	7/19 (36.84%)
Erythema ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	6/25 (24.00%)	0/3 (0.00%)	45/476 (9.45%)	2/10 (20.00%)	0/8 (0.00%)	0/6 (0.00%)	2/19 (10.53%)
Rash pruritic ^* 1	1/4 (25.00%)	1/3 (33.33%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	23/476 (4.83%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Night sweats ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	18/476 (3.78%)	1/10 (10.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Hyperhidrosis ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	17/476 (3.57%)	0/10 (0.00%)	2/8 (25.00%)	0/6 (0.00%)	1/19 (5.26%)
Urticaria ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	16/476 (3.36%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Rash erythematous ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	6/25 (24.00%)	1/3 (33.33%)	9/476 (1.89%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	1/19 (5.26%)
Pruritus generalised ^* 1	0/4 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	14/476 (2.94%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	1/19 (5.26%)
Alopecia ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	13/476 (2.73%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Swelling face ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	15/476 (3.15%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Rash macular ^* 1	3/4 (75.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	8/476 (1.68%)	0/10 (0.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Rash generalised ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	8/476 (1.68%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Eczema ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	1/8 (12.50%)	0/6 (0.00%)	0/19 (0.00%)
Skin lesion ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	6/476 (1.26%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Blister ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	5/476 (1.05%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/25 (4.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Skin hypopigmentation ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Vitiligo ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dermatitis exfoliative ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	3/476 (0.63%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dermatitis bullous ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Dermatitis contact ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Pain of skin ^* 1	1/4 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Skin discolouration ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Skin irritation ^* 1	0/4 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	2/476 (0.42%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Skin mass ^* 1	1/4 (25.00%)	0/3 (0.00%)	1/3 (33.33%)	0/25 (0.00%)	0/3 (0.00%)	1/476 (0.21%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Eczema asteatotic ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	1/10 (10.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
Keloid scar ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Rash vesicular ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Skin induration ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Vascular disorders
Hypotension ^* 1	1/4 (25.00%)	1/3 (33.33%)	1/3 (33.33%)	9/25 (36.00%)	0/3 (0.00%)	77/476 (16.18%)	3/10 (30.00%)	2/8 (25.00%)	2/6 (33.33%)	3/19 (15.79%)
Hypertension ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	0/3 (0.00%)	31/476 (6.51%)	1/10 (10.00%)	0/8 (0.00%)	1/6 (16.67%)	0/19 (0.00%)
Flushing ^* 1	3/4 (75.00%)	2/3 (66.67%)	1/3 (33.33%)	2/25 (8.00%)	0/3 (0.00%)	20/476 (4.20%)	0/10 (0.00%)	2/8 (25.00%)	1/6 (16.67%)	1/19 (5.26%)
Hot flush ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/25 (12.00%)	0/3 (0.00%)	10/476 (2.10%)	0/10 (0.00%)	1/8 (12.50%)	1/6 (16.67%)	0/19 (0.00%)
Embolism ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/25 (8.00%)	1/3 (33.33%)	4/476 (0.84%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	1/19 (5.26%)
Thrombophlebitis superficial ^* 1	0/4 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/25 (0.00%)	1/3 (33.33%)	0/476 (0.00%)	0/10 (0.00%)	0/8 (0.00%)	0/6 (0.00%)	0/19 (0.00%)
1 Term from vocabulary, MedDRA 19.0 * 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.

There are restrictions to the PI's rights to discuss or publish trial results.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Study Director
Organization:	Nektar Therapeutics
Phone:	855-482-8676
EMail:	StudyInquiry@nektar.com

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

Siefker-Radtke AO, Cho DC, Diab A, Sznol M, Bilen MA, Balar AV, Grignani G, Puente E, Tang L, Chien D, Hoch U, Choudhury A, Yu D, Currie SL, Tagliaferri MA, Zalevsky J, Hurwitz ME, Tannir NM. Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02. Eur Urol. 2022 Oct;82(4):365-373. doi: 10.1016/j.eururo.2022.05.002. Epub 2022 May 25.

Diab A, Tykodi SS, Daniels GA, Maio M, Curti BD, Lewis KD, Jang S, Kalinka E, Puzanov I, Spira AI, Cho DC, Guan S, Puente E, Nguyen T, Hoch U, Currie SL, Lin W, Tagliaferri MA, Zalevsky J, Sznol M, Hurwitz ME. Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma. J Clin Oncol. 2021 Sep 10;39(26):2914-2925. doi: 10.1200/JCO.21.00675. Epub 2021 Jul 13.

Veatch JR, Singhi N, Jesernig B, Paulson KG, Zalevsky J, Iaccucci E, Tykodi SS, Riddell SR. Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab. J Immunother Cancer. 2020 Dec;8(2):e001591. doi: 10.1136/jitc-2020-001591. Erratum In: J Immunother Cancer. 2021 Feb;9(2):

Layout table for additonal information

Responsible Party:	Nektar Therapeutics
ClinicalTrials.gov Identifier:	NCT02983045
Other Study ID Numbers:	16-214-02
First Submitted:	November 23, 2016
First Posted:	December 6, 2016
Results First Submitted:	November 29, 2022
Results First Posted:	March 13, 2023
Last Update Posted:	March 13, 2023

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