An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT02576509

Recruitment Status : Completed

First Posted : October 15, 2015

Results First Posted : June 26, 2020

Last Update Posted : March 19, 2024

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Sponsor:

Collaborator:

Ono Pharmaceutical Co. Ltd

Information provided by (Responsible Party):

Bristol-Myers Squibb

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Hepatocellular Carcinoma
Interventions	Drug: Nivolumab Drug: Sorafenib
Enrollment	743

Participant Flow

Recruitment Details
Pre-assignment Details	743 participants were assigned to treatment, and 730 treated. Reasons for 13 not treated: 2 requests to stop treatment; 6 withdrew consent; 5 no longer met study criteria


Arm/Group Title	Nivolumab 240 mg	Sorafenib 400 mg
Arm/Group Description	Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description	Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
Period Title: Pre-Treatment Period
Started ^[1]	371	372
Completed ^[2]	367	363
Not Completed	4	9
Reason Not Completed
Participant request to stop therapy	0	2
Participant withdrew consent	1	5
Participant no longer meets criteria	3	2
[1] Started = Assigned to treatment (randomized/enrolled) [2] Completed = Entering treatment period
Period Title: Treatment Period
Started ^[1]	367	363
Completed ^[2]	38	8
Not Completed	329	355
Reason Not Completed
Disease progression	245	240
Study drug toxicity	32	41
Death	1	1
Adverse event unrelated to study drug	37	40
Participant request to stop treatment	8	17
Participant withdrew consent	2	7
Lost to Follow-up	0	1
Maximum clinical benefit	1	0
Poor/non-compliance	0	1
Participant no longer meets criteria	1	0
Other reason	2	7
[1] Started = Received treatment [2] Completed = Continuing in the treatment period
Period Title: Follow-up Period
Started ^[1]	367	363
Completed ^[2]	318	311
Not Completed	49	52
Reason Not Completed
Death	41	35
Participant withdrew consent	7	14
Lost to Follow-up	0	1
Other reason	1	2
[1] Started = Received treatment [2] Completed = Continuing in the study

Baseline Characteristics

Arm/Group Title		Nivolumab 240 mg	Sorafenib 400 mg	Total
Arm/Group Description		Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...	Total of all reporting groups
Arm/Group Description		Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity	Total of all reporting groups
Overall Number of Baseline Participants		371	372	743
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	371 participants	372 participants	743 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	185 49.9%	176 47.3%	361 48.6%
	>=65 years	186 50.1%	196 52.7%	382 51.4%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	371 participants	372 participants	743 participants
		63.9 (10.61)	64.5 (10.91)	64.2 (10.76)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	371 participants	372 participants	743 participants
	Female	57 15.4%	55 14.8%	112 15.1%
	Male	314 84.6%	317 85.2%	631 84.9%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	371 participants	372 participants	743 participants
	Hispanic or Latino	5 1.3%	10 2.7%	15 2.0%
	Not Hispanic or Latino	180 48.5%	170 45.7%	350 47.1%
	Unknown or Not Reported	186 50.1%	192 51.6%	378 50.9%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	371 participants	372 participants	743 participants
	American Indian or Alaska Native	0 0.0%	1 0.3%	1 0.1%
	Asian	165 44.5%	167 44.9%	332 44.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 0.8%	2 0.5%	5 0.7%
	White	199 53.6%	196 52.7%	395 53.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	4 1.1%	6 1.6%	10 1.3%

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	OS is defined as the time from the date of randomization to the date o...
Description	OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates. Based on Kaplan-Meier Estimates.
Time Frame	time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)

Outcome Measure Data

Analysis Population Description

all randomized participants


Arm/Group Title	Nivolumab 240 mg	Sorafenib 400 mg
Arm/Group Description:	Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description:	Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed	371	372
Median (95% Confidence Interval) Unit of Measure: Months
	16.39 (13.93 to 18.37)	14.69 (11.89 to 17.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0752
	Comments	A priori threshold for statistical significance is 0.0419
	Method	Log Rank
	Comments	Log-rank Test stratified by the stratification factors as entered into the IVRS

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.71 to 1.02
	Estimation Comments	Nivolumab over Sorafenib; Stratified Cox proportional hazard model

Other Statistical Analysis		95.81% CI ADJUSTED FOR MULTIPLICITY: (0.72 to 1.02)

2.Secondary Outcome


Title	Objective Response Rate (ORR) Per BICR RECIST 1.1
Description	ORR is defined as the proportion of participants whose best overall re...
Description	ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later. Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors
Time Frame	the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)

Outcome Measure Data

Analysis Population Description

all randomized participants


Arm/Group Title	Nivolumab 240 mg	Sorafenib 400 mg
Arm/Group Description:	Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description:	Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed	371	372
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	15.4 (11.8 to 19.4)	7.0 (4.6 to 10.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	no test was performed due to OS p-value result above the prior threshold

Method of Estimation	Estimation Parameter	Difference of ORRs
	Estimated Value	8.3
	Confidence Interval	(2-Sided) 95% 3.9 to 12.7
	Estimation Comments	Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	no test was performed due to OS p-value result above the prior threshold

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.41
	Confidence Interval	(2-Sided) 95% 1.48 to 3.92
	Estimation Comments	Nivolumab over Sorafenib; Mantel-Haenszel estimator

3.Secondary Outcome


Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time from the date of randomization to the date ...
Description	PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.
Time Frame	time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months)

Outcome Measure Data

Analysis Population Description

all randomized participants


Arm/Group Title	Nivolumab 240 mg	Sorafenib 400 mg
Arm/Group Description:	Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description:	Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed	371	372
Median (95% Confidence Interval) Unit of Measure: Months
	3.68 (3.06 to 3.88)	3.75 (3.71 to 4.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	no test was performed due to OS p-value result above the prior threshold

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.79 to 1.10
	Estimation Comments	Nivolumab over Sorafenib; Stratified Cox proportional hazard model

4.Secondary Outcome


Title	Efficacy Based on PD-L1 Expression - OS and PFS
Description	PD-L1 expression is defined as the percent of tumor cell membrane stai...
Description	PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: PD-L1 > X %: ≥ X % PD-L1 expression PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.
Time Frame	the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)

Outcome Measure Data

Analysis Population Description

all randomized participants with a >=1% PD-L1 expression all randomized participants with a <1% PD-L1 expression all randomized participants without PD-L1 quantifiable


Arm/Group Title		Nivolumab 240 mg	Sorafenib 400 mg
Arm/Group Description:		Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description:		Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed		371	372
Median (95% Confidence Interval) Unit of Measure: Months
>=1%, OS	Number Analyzed	71 participants	64 participants
>=1%, OS		16.07 (8.41 to 22.34)	8.62 (5.72 to 16.30)
>=1%, PFS	Number Analyzed	71 participants	64 participants
>=1%, PFS		3.84 (2.10 to 7.62)	3.58 (1.97 to 5.36)
<1%, OS	Number Analyzed	295 participants	300 participants
<1%, OS		16.72 (13.93 to 18.56)	15.24 (12.58 to 18.10)
<1%, PFS	Number Analyzed	295 participants	300 participants
<1%, PFS		3.61 (2.43 to 3.81)	3.75 (3.71 to 5.32)
without PD-L1 quantifiable, OS	Number Analyzed	5 participants	8 participants
without PD-L1 quantifiable, OS		16.23 ^[1] (5.82 to NA)	22.05 ^[1] (1.77 to NA)
without PD-L1 quantifiable, PFS	Number Analyzed	5 participants	8 participants
without PD-L1 quantifiable, PFS		2.00 ^[1] (1.87 to NA)	6.13 (1.08 to 11.17)

[1]

Upper limit cannot be estimated based on the data

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	PD-L1 >= 1%, OS; no test was performed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.54 to 1.19
	Estimation Comments	Nivolumab over Sorafenib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	PD-L1 >=1%, PFS; no test was performed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.48 to 1.03
	Estimation Comments	Nivolumab over Sorafenib

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	PD-L1 <1%, OS; no test was performed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% 0.69 to 1.02
	Estimation Comments	Nivolumab over Sorafenib

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	PD-L1 <1%, PFS; no test was performed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.81 to 1.17
	Estimation Comments	Nivolumab over Sorafenib

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	without PD-L1 quantifiable, OS; no test was performed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95% 0.34 to 4.74
	Estimation Comments	Nivolumab over Sorafenib

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	without PD-L1 quantifiable, PFS; no test was performed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.27 to 3.52
	Estimation Comments	Nivolumab over Sorafenib

5.Secondary Outcome


Title	Efficacy Based on PD-L1 Expression - ORR
Description	PD-L1 expression is defined as the percent of tumor cell membrane stai...
Description	PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: PD-L1 > X %: ≥ X % PD-L1 expression PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.
Time Frame	the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)

Outcome Measure Data

Analysis Population Description

all randomized participants with a >=1% PD-L1 expression all randomized participants with a <1% PD-L1 expression all randomized participants without PD-L1 quantifiable Note: odds ratio for participants without PD-L1 quantifiable cannot be estimated based on the data


Arm/Group Title		Nivolumab 240 mg	Sorafenib 400 mg
Arm/Group Description:		Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description:		Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
Overall Number of Participants Analyzed		371	372
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
>=1%, ORR	Number Analyzed	71 participants	64 participants
>=1%, ORR		28.2 (18.1 to 40.1)	9.4 (3.5 to 19.3)
<1%, ORR	Number Analyzed	295 participants	300 participants
<1%, ORR		12.2 (8.7 to 16.5)	6.7 (4.1 to 10.1)
without PD-L1 quantifiable, ORR	Number Analyzed	5 participants	8 participants
without PD-L1 quantifiable, ORR		20.0 (0.5 to 71.6)	0.0 (0.0 to 36.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	PD-L1 >=1%, ORR; no test was performed

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.79
	Confidence Interval	(2-Sided) 95% 1.41 to 10.17
	Estimation Comments	Odds ratio (Nivolumab over Sorafenib) and associated unstratified 95% exact CI.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nivolumab 240 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	PD-L1 <1%, ORR; no test was performed

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.95
	Confidence Interval	(2-Sided) 95% 1.10 to 3.45
	Estimation Comments	Odds ratio (Nivolumab over Sorafenib) and associated unstratified 95% exact CI

Adverse Events

Time Frame	Includes events reported between first dose and 100 days after last dose of study therapy, assessed up to June 2019 (approximately 3 and a half years).
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	NIVOLUMAB 240 mg	SORAFENIB 400 mg
Arm/Group Description	Nivolumab 240 mg IV every 2 weeks u...	Sorafenib 400 mg PO BID until disea...
Arm/Group Description	Nivolumab 240 mg IV every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg PO BID until disease progression or unacceptable toxicity
All-Cause Mortality
	NIVOLUMAB 240 mg	SORAFENIB 400 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	242/367 (65.94%)	270/363 (74.38%)
Serious Adverse Events Serious Adverse Events
	NIVOLUMAB 240 mg	SORAFENIB 400 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	207/367 (56.40%)	214/363 (58.95%)
Blood and lymphatic system disorders
Anaemia ^† 1	8/367 (2.18%)	6/363 (1.65%)
Febrile neutropenia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Iron deficiency anaemia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Neutropenia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Cardiac disorders
Acute coronary syndrome ^† 1	0/367 (0.00%)	1/363 (0.28%)
Aortic valve incompetence ^† 1	1/367 (0.27%)	0/363 (0.00%)
Atrial fibrillation ^† 1	5/367 (1.36%)	0/363 (0.00%)
Cardiac arrest ^† 1	1/367 (0.27%)	0/363 (0.00%)
Cardiac failure ^† 1	0/367 (0.00%)	1/363 (0.28%)
Cardiac failure acute ^† 1	2/367 (0.54%)	0/363 (0.00%)
Myocardial infarction ^† 1	2/367 (0.54%)	1/363 (0.28%)
Pericardial effusion ^† 1	1/367 (0.27%)	0/363 (0.00%)
Pericarditis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Sinus tachycardia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Endocrine disorders
Adrenal insufficiency ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hypophysitis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Eye disorders
Amblyopia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Cataract ^† 1	0/367 (0.00%)	1/363 (0.28%)
Eyelid function disorder ^† 1	1/367 (0.27%)	0/363 (0.00%)
Glaucoma ^† 1	0/367 (0.00%)	1/363 (0.28%)
Retinal vascular disorder ^† 1	0/367 (0.00%)	1/363 (0.28%)
Gastrointestinal disorders
Abdominal distension ^† 1	0/367 (0.00%)	1/363 (0.28%)
Abdominal pain ^† 1	7/367 (1.91%)	11/363 (3.03%)
Abdominal pain lower ^† 1	1/367 (0.27%)	0/363 (0.00%)
Abdominal pain upper ^† 1	2/367 (0.54%)	5/363 (1.38%)
Anal fistula ^† 1	0/367 (0.00%)	1/363 (0.28%)
Ascites ^† 1	7/367 (1.91%)	7/363 (1.93%)
Colitis ^† 1	5/367 (1.36%)	0/363 (0.00%)
Colitis ulcerative ^† 1	1/367 (0.27%)	0/363 (0.00%)
Diaphragmatic hernia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Diarrhoea ^† 1	4/367 (1.09%)	1/363 (0.28%)
Diverticulum intestinal ^† 1	1/367 (0.27%)	0/363 (0.00%)
Duodenitis haemorrhagic ^† 1	1/367 (0.27%)	0/363 (0.00%)
Dysphagia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Gastric ulcer ^† 1	0/367 (0.00%)	1/363 (0.28%)
Gastric varices ^† 1	0/367 (0.00%)	1/363 (0.28%)
Gastritis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Gastrointestinal disorder ^† 1	0/367 (0.00%)	1/363 (0.28%)
Gastrointestinal haemorrhage ^† 1	6/367 (1.63%)	6/363 (1.65%)
Gastrointestinal perforation ^† 1	1/367 (0.27%)	0/363 (0.00%)
Haematemesis ^† 1	1/367 (0.27%)	2/363 (0.55%)
Inguinal hernia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Intra-abdominal haemorrhage ^† 1	1/367 (0.27%)	1/363 (0.28%)
Lower gastrointestinal haemorrhage ^† 1	1/367 (0.27%)	0/363 (0.00%)
Nausea ^† 1	0/367 (0.00%)	2/363 (0.55%)
Oesophageal haemorrhage ^† 1	0/367 (0.00%)	1/363 (0.28%)
Oesophageal varices haemorrhage ^† 1	4/367 (1.09%)	7/363 (1.93%)
Pancreatitis ^† 1	2/367 (0.54%)	1/363 (0.28%)
Pancreatitis acute ^† 1	0/367 (0.00%)	1/363 (0.28%)
Splenic artery aneurysm ^† 1	1/367 (0.27%)	0/363 (0.00%)
Stomatitis ^† 1	2/367 (0.54%)	0/363 (0.00%)
Upper gastrointestinal haemorrhage ^† 1	4/367 (1.09%)	6/363 (1.65%)
Varices oesophageal ^† 1	3/367 (0.82%)	2/363 (0.55%)
Vomiting ^† 1	0/367 (0.00%)	3/363 (0.83%)
General disorders
Asthenia ^† 1	0/367 (0.00%)	3/363 (0.83%)
Chest discomfort ^† 1	1/367 (0.27%)	0/363 (0.00%)
Death ^† 1	0/367 (0.00%)	2/363 (0.55%)
Fatigue ^† 1	1/367 (0.27%)	4/363 (1.10%)
General physical health deterioration ^† 1	9/367 (2.45%)	15/363 (4.13%)
Hypothermia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Influenza like illness ^† 1	1/367 (0.27%)	0/363 (0.00%)
Mucosal inflammation ^† 1	1/367 (0.27%)	0/363 (0.00%)
Multiple organ dysfunction syndrome ^† 1	3/367 (0.82%)	0/363 (0.00%)
Non-cardiac chest pain ^† 1	1/367 (0.27%)	0/363 (0.00%)
Oedema peripheral ^† 1	1/367 (0.27%)	0/363 (0.00%)
Pain ^† 1	1/367 (0.27%)	0/363 (0.00%)
Performance status decreased ^† 1	1/367 (0.27%)	1/363 (0.28%)
Pyrexia ^† 1	7/367 (1.91%)	6/363 (1.65%)
Sudden death ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hepatobiliary disorders
Acute hepatic failure ^† 1	0/367 (0.00%)	1/363 (0.28%)
Autoimmune hepatitis ^† 1	3/367 (0.82%)	0/363 (0.00%)
Bile duct obstruction ^† 1	1/367 (0.27%)	1/363 (0.28%)
Bile duct stenosis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Biliary dilatation ^† 1	0/367 (0.00%)	1/363 (0.28%)
Biloma ^† 1	1/367 (0.27%)	0/363 (0.00%)
Cholangitis ^† 1	4/367 (1.09%)	4/363 (1.10%)
Cholecystitis ^† 1	0/367 (0.00%)	2/363 (0.55%)
Cholecystitis acute ^† 1	0/367 (0.00%)	1/363 (0.28%)
Cholestasis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Haemobilia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hepatic cirrhosis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hepatic failure ^† 1	10/367 (2.72%)	7/363 (1.93%)
Hepatic function abnormal ^† 1	1/367 (0.27%)	2/363 (0.55%)
Hepatic haemorrhage ^† 1	1/367 (0.27%)	1/363 (0.28%)
Hepatic lesion ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hepatocellular injury ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hepatorenal syndrome ^† 1	0/367 (0.00%)	3/363 (0.83%)
Hepatotoxicity ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hyperbilirubinaemia ^† 1	3/367 (0.82%)	2/363 (0.55%)
Jaundice ^† 1	2/367 (0.54%)	0/363 (0.00%)
Jaundice cholestatic ^† 1	2/367 (0.54%)	1/363 (0.28%)
Liver injury ^† 1	0/367 (0.00%)	1/363 (0.28%)
Infections and infestations
Abdominal infection ^† 1	0/367 (0.00%)	2/363 (0.55%)
Abscess limb ^† 1	1/367 (0.27%)	0/363 (0.00%)
Anal abscess ^† 1	1/367 (0.27%)	2/363 (0.55%)
Arthritis bacterial ^† 1	0/367 (0.00%)	1/363 (0.28%)
Bacterial infection ^† 1	0/367 (0.00%)	1/363 (0.28%)
Bacterial sepsis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Biliary sepsis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Biliary tract infection ^† 1	1/367 (0.27%)	0/363 (0.00%)
Brain abscess ^† 1	0/367 (0.00%)	1/363 (0.28%)
Cellulitis ^† 1	0/367 (0.00%)	2/363 (0.55%)
Diverticulitis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Epididymitis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Erysipelas ^† 1	2/367 (0.54%)	0/363 (0.00%)
Escherichia bacteraemia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Escherichia sepsis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Gastroenteritis ^† 1	1/367 (0.27%)	1/363 (0.28%)
Genitourinary tract infection ^† 1	0/367 (0.00%)	1/363 (0.28%)
Haematoma infection ^† 1	0/367 (0.00%)	1/363 (0.28%)
Herpes simplex ^† 1	1/367 (0.27%)	0/363 (0.00%)
Infection ^† 1	1/367 (0.27%)	1/363 (0.28%)
Infective exacerbation of chronic obstructive airways disease ^† 1	1/367 (0.27%)	0/363 (0.00%)
Klebsiella sepsis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Liver abscess ^† 1	0/367 (0.00%)	2/363 (0.55%)
Lower respiratory tract infection ^† 1	2/367 (0.54%)	0/363 (0.00%)
Lung infection ^† 1	1/367 (0.27%)	0/363 (0.00%)
Osteomyelitis acute ^† 1	1/367 (0.27%)	0/363 (0.00%)
Perirectal abscess ^† 1	0/367 (0.00%)	1/363 (0.28%)
Peritonitis ^† 1	0/367 (0.00%)	2/363 (0.55%)
Peritonitis bacterial ^† 1	2/367 (0.54%)	0/363 (0.00%)
Pneumocystis jirovecii pneumonia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Pneumonia ^† 1	4/367 (1.09%)	4/363 (1.10%)
Pneumonia klebsiella ^† 1	0/367 (0.00%)	1/363 (0.28%)
Pneumonia mycoplasmal ^† 1	1/367 (0.27%)	0/363 (0.00%)
Pulmonary tuberculosis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Rhinovirus infection ^† 1	1/367 (0.27%)	0/363 (0.00%)
Sepsis ^† 1	7/367 (1.91%)	2/363 (0.55%)
Septic shock ^† 1	0/367 (0.00%)	2/363 (0.55%)
Tooth abscess ^† 1	1/367 (0.27%)	0/363 (0.00%)
Tracheitis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Upper respiratory tract infection ^† 1	2/367 (0.54%)	1/363 (0.28%)
Urinary tract infection ^† 1	0/367 (0.00%)	2/363 (0.55%)
Viral pharyngitis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Virologic failure ^† 1	1/367 (0.27%)	0/363 (0.00%)
Wound infection ^† 1	0/367 (0.00%)	1/363 (0.28%)
Injury, poisoning and procedural complications
Exposure to communicable disease ^† 1	1/367 (0.27%)	0/363 (0.00%)
Fracture ^† 1	0/367 (0.00%)	1/363 (0.28%)
Head injury ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hepatic rupture ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hip fracture ^† 1	0/367 (0.00%)	1/363 (0.28%)
Humerus fracture ^† 1	1/367 (0.27%)	1/363 (0.28%)
Infusion related reaction ^† 1	3/367 (0.82%)	0/363 (0.00%)
Meniscus injury ^† 1	1/367 (0.27%)	0/363 (0.00%)
Overdose ^† 1	1/367 (0.27%)	2/363 (0.55%)
Periprosthetic fracture ^† 1	0/367 (0.00%)	1/363 (0.28%)
Post procedural complication ^† 1	0/367 (0.00%)	1/363 (0.28%)
Procedural pain ^† 1	0/367 (0.00%)	1/363 (0.28%)
Road traffic accident ^† 1	1/367 (0.27%)	1/363 (0.28%)
Spinal fracture ^† 1	1/367 (0.27%)	0/363 (0.00%)
Subdural haemorrhage ^† 1	1/367 (0.27%)	0/363 (0.00%)
Upper limb fracture ^† 1	1/367 (0.27%)	1/363 (0.28%)
Investigations
Blood bilirubin increased ^† 1	1/367 (0.27%)	1/363 (0.28%)
Blood creatinine increased ^† 1	1/367 (0.27%)	0/363 (0.00%)
General physical condition abnormal ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hepatic enzyme increased ^† 1	1/367 (0.27%)	0/363 (0.00%)
Influenza A virus test positive ^† 1	1/367 (0.27%)	0/363 (0.00%)
Liver function test abnormal ^† 1	1/367 (0.27%)	0/363 (0.00%)
Liver function test increased ^† 1	2/367 (0.54%)	0/363 (0.00%)
Occult blood positive ^† 1	1/367 (0.27%)	0/363 (0.00%)
Platelet count decreased ^† 1	0/367 (0.00%)	1/363 (0.28%)
Transaminases increased ^† 1	3/367 (0.82%)	0/363 (0.00%)
Metabolism and nutrition disorders
Cachexia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Cell death ^† 1	1/367 (0.27%)	1/363 (0.28%)
Decreased appetite ^† 1	0/367 (0.00%)	4/363 (1.10%)
Dehydration ^† 1	1/367 (0.27%)	2/363 (0.55%)
Diabetes mellitus ^† 1	1/367 (0.27%)	0/363 (0.00%)
Failure to thrive ^† 1	0/367 (0.00%)	1/363 (0.28%)
Fulminant type 1 diabetes mellitus ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hyperglycaemia ^† 1	3/367 (0.82%)	0/363 (0.00%)
Hyperkalaemia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hyperlipasaemia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hypoglycaemia ^† 1	2/367 (0.54%)	0/363 (0.00%)
Hypokalaemia ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hyponatraemia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Ketoacidosis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Lactic acidosis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Musculoskeletal and connective tissue disorders
Arthropathy ^† 1	1/367 (0.27%)	0/363 (0.00%)
Back pain ^† 1	2/367 (0.54%)	1/363 (0.28%)
Bone pain ^† 1	0/367 (0.00%)	2/363 (0.55%)
Fistula ^† 1	1/367 (0.27%)	0/363 (0.00%)
Flank pain ^† 1	0/367 (0.00%)	1/363 (0.28%)
Intervertebral disc compression ^† 1	1/367 (0.27%)	0/363 (0.00%)
Joint swelling ^† 1	1/367 (0.27%)	0/363 (0.00%)
Muscular weakness ^† 1	3/367 (0.82%)	0/363 (0.00%)
Musculoskeletal pain ^† 1	2/367 (0.54%)	0/363 (0.00%)
Osteoarthritis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Pain in extremity ^† 1	1/367 (0.27%)	0/363 (0.00%)
Pathological fracture ^† 1	0/367 (0.00%)	1/363 (0.28%)
Rhabdomyolysis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	0/367 (0.00%)	1/363 (0.28%)
Cancer pain ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hepatocellular carcinoma ^† 1	0/367 (0.00%)	2/363 (0.55%)
Liver carcinoma ruptured ^† 1	4/367 (1.09%)	2/363 (0.55%)
Malignant neoplasm of spinal cord ^† 1	1/367 (0.27%)	0/363 (0.00%)
Malignant neoplasm progression ^† 1	67/367 (18.26%)	70/363 (19.28%)
Metastases to bone ^† 1	2/367 (0.54%)	0/363 (0.00%)
Metastases to central nervous system ^† 1	1/367 (0.27%)	0/363 (0.00%)
Metastases to liver ^† 1	1/367 (0.27%)	0/363 (0.00%)
Metastases to spinal cord ^† 1	1/367 (0.27%)	0/363 (0.00%)
Neoplasm malignant ^† 1	0/367 (0.00%)	1/363 (0.28%)
Prostate cancer ^† 1	0/367 (0.00%)	1/363 (0.28%)
Rectal adenocarcinoma ^† 1	1/367 (0.27%)	0/363 (0.00%)
Squamous cell carcinoma ^† 1	0/367 (0.00%)	4/363 (1.10%)
Transitional cell carcinoma ^† 1	0/367 (0.00%)	1/363 (0.28%)
Tumour associated fever ^† 1	1/367 (0.27%)	0/363 (0.00%)
Tumour haemorrhage ^† 1	1/367 (0.27%)	1/363 (0.28%)
Tumour thrombosis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Nervous system disorders
Altered state of consciousness ^† 1	1/367 (0.27%)	0/363 (0.00%)
Cerebral haemorrhage ^† 1	3/367 (0.82%)	0/363 (0.00%)
Cerebral infarction ^† 1	0/367 (0.00%)	1/363 (0.28%)
Cerebrovascular accident ^† 1	1/367 (0.27%)	2/363 (0.55%)
Cognitive disorder ^† 1	0/367 (0.00%)	1/363 (0.28%)
Encephalopathy ^† 1	0/367 (0.00%)	4/363 (1.10%)
Epilepsy ^† 1	0/367 (0.00%)	1/363 (0.28%)
Haemorrhage intracranial ^† 1	1/367 (0.27%)	1/363 (0.28%)
Headache ^† 1	0/367 (0.00%)	2/363 (0.55%)
Hemiparesis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Hepatic encephalopathy ^† 1	6/367 (1.63%)	5/363 (1.38%)
Hypoglycaemic coma ^† 1	0/367 (0.00%)	1/363 (0.28%)
Neuritis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Neuropathy peripheral ^† 1	0/367 (0.00%)	1/363 (0.28%)
Spinal cord compression ^† 1	1/367 (0.27%)	0/363 (0.00%)
Subarachnoid haemorrhage ^† 1	1/367 (0.27%)	0/363 (0.00%)
Transient ischaemic attack ^† 1	0/367 (0.00%)	1/363 (0.28%)
Psychiatric disorders
Assisted suicide ^† 1	0/367 (0.00%)	1/363 (0.28%)
Confusional state ^† 1	0/367 (0.00%)	1/363 (0.28%)
Depression ^† 1	0/367 (0.00%)	1/363 (0.28%)
Suicide attempt ^† 1	0/367 (0.00%)	1/363 (0.28%)
Renal and urinary disorders
Acute kidney injury ^† 1	1/367 (0.27%)	5/363 (1.38%)
Diabetic nephropathy ^† 1	0/367 (0.00%)	1/363 (0.28%)
Renal failure ^† 1	1/367 (0.27%)	1/363 (0.28%)
Urinary retention ^† 1	1/367 (0.27%)	1/363 (0.28%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema ^† 1	1/367 (0.27%)	0/363 (0.00%)
Atelectasis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Dyspnoea ^† 1	3/367 (0.82%)	2/363 (0.55%)
Interstitial lung disease ^† 1	2/367 (0.54%)	0/363 (0.00%)
Lung consolidation ^† 1	1/367 (0.27%)	0/363 (0.00%)
Nasal ulcer ^† 1	0/367 (0.00%)	1/363 (0.28%)
Pleural effusion ^† 1	2/367 (0.54%)	1/363 (0.28%)
Pleurisy ^† 1	1/367 (0.27%)	0/363 (0.00%)
Pneumonitis ^† 1	4/367 (1.09%)	0/363 (0.00%)
Pneumothorax ^† 1	0/367 (0.00%)	1/363 (0.28%)
Pulmonary embolism ^† 1	1/367 (0.27%)	3/363 (0.83%)
Pulmonary oedema ^† 1	1/367 (0.27%)	0/363 (0.00%)
Respiratory distress ^† 1	0/367 (0.00%)	1/363 (0.28%)
Respiratory failure ^† 1	1/367 (0.27%)	1/363 (0.28%)
Skin and subcutaneous tissue disorders
Blister ^† 1	1/367 (0.27%)	0/363 (0.00%)
Dermatitis bullous ^† 1	1/367 (0.27%)	0/363 (0.00%)
Drug reaction with eosinophilia and systemic symptoms ^† 1	1/367 (0.27%)	0/363 (0.00%)
Erythema multiforme ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hyperkeratosis ^† 1	0/367 (0.00%)	1/363 (0.28%)
Leukoplakia ^† 1	1/367 (0.27%)	0/363 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome ^† 1	1/367 (0.27%)	2/363 (0.55%)
Pruritus ^† 1	1/367 (0.27%)	1/363 (0.28%)
Rash ^† 1	2/367 (0.54%)	2/363 (0.55%)
Rash erythematous ^† 1	1/367 (0.27%)	0/363 (0.00%)
Rash maculo-papular ^† 1	2/367 (0.54%)	0/363 (0.00%)
Skin reaction ^† 1	1/367 (0.27%)	0/363 (0.00%)
Stevens-Johnson syndrome ^† 1	2/367 (0.54%)	0/363 (0.00%)
Toxic epidermal necrolysis ^† 1	1/367 (0.27%)	0/363 (0.00%)
Vascular disorders
Bleeding varicose vein ^† 1	1/367 (0.27%)	1/363 (0.28%)
Haemorrhage ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hypotension ^† 1	0/367 (0.00%)	1/363 (0.28%)
Hypovolaemic shock ^† 1	1/367 (0.27%)	0/363 (0.00%)
1 Term from vocabulary, 22.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	NIVOLUMAB 240 mg	SORAFENIB 400 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	339/367 (92.37%)	352/363 (96.97%)
Blood and lymphatic system disorders
Anaemia ^† 1	32/367 (8.72%)	30/363 (8.26%)
Endocrine disorders
Hypothyroidism ^† 1	28/367 (7.63%)	12/363 (3.31%)
Gastrointestinal disorders
Abdominal distension ^† 1	14/367 (3.81%)	22/363 (6.06%)
Abdominal pain ^† 1	67/367 (18.26%)	82/363 (22.59%)
Abdominal pain upper ^† 1	40/367 (10.90%)	49/363 (13.50%)
Ascites ^† 1	44/367 (11.99%)	44/363 (12.12%)
Constipation ^† 1	49/367 (13.35%)	53/363 (14.60%)
Diarrhoea ^† 1	98/367 (26.70%)	191/363 (52.62%)
Nausea ^† 1	60/367 (16.35%)	70/363 (19.28%)
Stomatitis ^† 1	16/367 (4.36%)	25/363 (6.89%)
Vomiting ^† 1	35/367 (9.54%)	40/363 (11.02%)
General disorders
Asthenia ^† 1	40/367 (10.90%)	43/363 (11.85%)
Fatigue ^† 1	102/367 (27.79%)	117/363 (32.23%)
Oedema peripheral ^† 1	41/367 (11.17%)	40/363 (11.02%)
Pyrexia ^† 1	65/367 (17.71%)	58/363 (15.98%)
Infections and infestations
Nasopharyngitis ^† 1	31/367 (8.45%)	23/363 (6.34%)
Upper respiratory tract infection ^† 1	26/367 (7.08%)	15/363 (4.13%)
Injury, poisoning and procedural complications
Infusion related reaction ^† 1	21/367 (5.72%)	0/363 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	51/367 (13.90%)	40/363 (11.02%)
Amylase increased ^† 1	24/367 (6.54%)	14/363 (3.86%)
Aspartate aminotransferase increased ^† 1	81/367 (22.07%)	61/363 (16.80%)
Blood alkaline phosphatase increased ^† 1	19/367 (5.18%)	17/363 (4.68%)
Blood bilirubin increased ^† 1	40/367 (10.90%)	48/363 (13.22%)
Lipase increased ^† 1	36/367 (9.81%)	26/363 (7.16%)
Platelet count decreased ^† 1	17/367 (4.63%)	28/363 (7.71%)
Weight decreased ^† 1	32/367 (8.72%)	68/363 (18.73%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	76/367 (20.71%)	135/363 (37.19%)
Hyperglycaemia ^† 1	21/367 (5.72%)	8/363 (2.20%)
Hypoalbuminaemia ^† 1	19/367 (5.18%)	31/363 (8.54%)
Hypokalaemia ^† 1	13/367 (3.54%)	20/363 (5.51%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	41/367 (11.17%)	21/363 (5.79%)
Back pain ^† 1	37/367 (10.08%)	34/363 (9.37%)
Muscle spasms ^† 1	14/367 (3.81%)	29/363 (7.99%)
Musculoskeletal pain ^† 1	17/367 (4.63%)	19/363 (5.23%)
Nervous system disorders
Dizziness ^† 1	19/367 (5.18%)	13/363 (3.58%)
Headache ^† 1	21/367 (5.72%)	33/363 (9.09%)
Psychiatric disorders
Insomnia ^† 1	28/367 (7.63%)	32/363 (8.82%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	44/367 (11.99%)	46/363 (12.67%)
Dysphonia ^† 1	10/367 (2.72%)	50/363 (13.77%)
Dyspnoea ^† 1	26/367 (7.08%)	23/363 (6.34%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	6/367 (1.63%)	72/363 (19.83%)
Dry skin ^† 1	15/367 (4.09%)	21/363 (5.79%)
Erythema ^† 1	5/367 (1.36%)	31/363 (8.54%)
Palmar-plantar erythrodysaesthesia syndrome ^† 1	29/367 (7.90%)	181/363 (49.86%)
Pruritus ^† 1	82/367 (22.34%)	49/363 (13.50%)
Rash ^† 1	70/367 (19.07%)	57/363 (15.70%)
Vascular disorders
Hypertension ^† 1	32/367 (8.72%)	85/363 (23.42%)
1 Term from vocabulary, 22.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Results Point of Contact

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

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

Li Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022 Nov 15;128(22):3995-4003. doi: 10.1002/cncr.34457. Epub 2022 Sep 16.

Shi J, Liu J, Tu X, Li B, Tong Z, Wang T, Zheng Y, Shi H, Zeng X, Chen W, Yin W, Fang W. Single-cell immune signature for detecting early-stage HCC and early assessing anti-PD-1 immunotherapy efficacy. J Immunother Cancer. 2022 Jan;10(1):e003133. doi: 10.1136/jitc-2021-003133.

Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, Kudo M, Harding JJ, Merle P, Rosmorduc O, Wyrwicz L, Schott E, Choo SP, Kelley RK, Sieghart W, Assenat E, Zaucha R, Furuse J, Abou-Alfa GK, El-Khoueiry AB, Melero I, Begic D, Chen G, Neely J, Wisniewski T, Tschaika M, Sangro B. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022 Jan;23(1):77-90. doi: 10.1016/S1470-2045(21)00604-5. Epub 2021 Dec 13.

Layout table for additonal information

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02576509
Other Study ID Numbers:	CA209-459
First Submitted:	October 13, 2015
First Posted:	October 15, 2015
Results First Submitted:	May 29, 2020
Results First Posted:	June 26, 2020
Last Update Posted:	March 19, 2024

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