A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy Alone in First Line NSCLC (CheckMate 9LA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03215706

Recruitment Status : Active, not recruiting

First Posted : July 12, 2017

Results First Posted : September 16, 2020

Last Update Posted : January 10, 2024

View this study on the modernized ClinicalTrials.gov

Sponsor:

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	Non-Small Cell Lung Cancer
Interventions	Biological: Ipilimumab Biological: Nivolumab Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed Drug: Cisplatin
Enrollment	719

Participant Flow

Recruitment Details
Pre-assignment Details	719 Randomized; 707 Treated; reasons not treated: 1 adverse event unrelated to the study drug, 4 participants withdrew consent, 5 no longer meet study criteria and 2 other reasons.


Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Period Title: Randomization
Started ^[1]	361	358
Completed ^[2]	358	349
Not Completed	3	9
Reason Not Completed
Adverse Event unrelated to study drug	1	0
participant withdrew consent	1	3
no longer meets study criteria	1	4
other reasons	0	2
[1] = Participants Randomized [2] = Participants treated
Period Title: Treatment Period
Started ^[1]	358	349
Completed ^[2]	16	103
Not Completed	342	246
Reason Not Completed
Disease Progression	150	142
Study Drug Toxicity	53	21
Death	2	1
Adverse event unrelated to study drug	24	23
Request to D/C treatment	1	6
Participant withdrew consent	3	4
Lost to Follow-up	0	1
Other Reasons	4	5
Ongoing in the treatment period	105	43
[1] = Participants treated [2] = completing treatment

Baseline Characteristics

Arm/Group Title		Treatment A	Treatment B	Total
Arm/Group Description		Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only	Total of all reporting groups
Arm/Group Description		Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only	Total of all reporting groups
Overall Number of Baseline Participants		361	358	719
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Standard Deviation) Unit of measure: Years
	Number Analyzed	361 participants	358 participants	719 participants
		65.0 (8.3)	65.0 (10.3)	65.0 (9.4)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	361 participants	358 participants	719 participants
˂65 years old		176 48.8%	178 49.7%	354 49.2%
≥65 and ˂75 years old		148 41.0%	147 41.1%	295 41.0%
≥75 years old		37 10.2%	33 9.2%	70 9.7%
≥85 years old		0 0.0%	2 0.6%	2 0.3%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	361 participants	358 participants	719 participants
	Female	109 30.2%	106 29.6%	215 29.9%
	Male	252 69.8%	252 70.4%	504 70.1%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	361 participants	358 participants	719 participants
	Hispanic or Latino	29 8.0%	31 8.7%	60 8.3%
	Not Hispanic or Latino	154 42.7%	158 44.1%	312 43.4%
	Unknown or Not Reported	178 49.3%	169 47.2%	347 48.3%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	361 participants	358 participants	719 participants
	American Indian or Alaska Native	1 0.3%	0 0.0%	1 0.1%
	Asian	30 8.3%	30 8.4%	60 8.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	5 1.4%	4 1.1%	9 1.3%
	White	322 89.2%	316 88.3%	638 88.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	3 0.8%	8 2.2%	11 1.5%

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to the date of death fro...
Description	OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Time Frame	From date of randomization to date of death (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants, Global Population


Arm/Group Title	Treatment A	Treatment B
Arm/Group Description:	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed	361	358
Median (95% Confidence Interval) Unit of Measure: Months
	14.13 (13.24 to 16.16)	10.74 (9.46 to 12.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Treatment A over Treatment B

Statistical Test of Hypothesis	P-Value	0.0006
	Comments	[Not Specified]
	Method	Log-rank test stratified
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95% 0.56 to 0.86
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression Free Survival (PFS) by BICR
Description	PFS (primary definition) was defined as the time from the randomizatio...
Description	PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
Time Frame	From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants, Global Population


Arm/Group Title	Treatment A	Treatment B
Arm/Group Description:	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed	361	358
Median (95% Confidence Interval) Unit of Measure: Months
	6.83 (5.55 to 7.66)	4.96 (4.27 to 5.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Treatment A over Treatment B

Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Log-rank test stratified
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95% 0.58 to 0.84
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR) by BICR
Description	ORR was defined as the number of randomized participants with a best o...
Description	ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression.
Time Frame	From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants, Global Population


Arm/Group Title	Treatment A	Treatment B
Arm/Group Description:	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed	361	358
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of Participants
	37.7 (32.7 to 42.9)	25.1 (20.7 to 30.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Treatment A over Treatment B

Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	Mantel Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 95% 1.31 to 2.50
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Duration of Response (DoR)
Description	DoR was defined as the time between the date of first confirmed docume...
Description	DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only.
Time Frame	From date of first confirmed response to date of tumor progression (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All confirmed Responders, Global Population


Arm/Group Title	Treatment A	Treatment B
Arm/Group Description:	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed	136	90
Median (95% Confidence Interval) Unit of Measure: Months
	10.02 (8.21 to 13.01)	5.09 (4.34 to 7.00)

5.Secondary Outcome


Title	Time to Response (TTR)
Description	TTR was defined as the time from randomization to the date of the firs...
Description	TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only.
Time Frame	From date of randomization to date of first confirmed documented response (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Confirmed Responders, Global Population


Arm/Group Title	Treatment A	Treatment B
Arm/Group Description:	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed	136	90
Median (Full Range) Unit of Measure: Months
	2.51 (1.1 to 10.6)	1.56 (1.2 to 8.3)

6.Secondary Outcome


Title	Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression
Description	PD-L1 expression was defined as the percent of tumor cells with membra...
Description	PD-L1 expression was defined as the percent of tumor cells with membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC 28-8 pharmDx test. PD-L1 expression was classified as PD-L1 ≥1% (≥1% tumor cells with membrane staining in a minimum of a hundred evaluable tumor cells), PD-L1 < 1% and PD-L1 not quantifiable (without quantifiable PD-L1 expression), PD-L1 expression ≥ 50%, PD-L1 expression 1 to 49%
Time Frame	From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants, Global Population


Arm/Group Title		Treatment A	Treatment B
Arm/Group Description:		Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:		Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed		361	358
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of Participants
BASELINE PD-L1 EXPRESSION ≥1%	Number Analyzed	203 participants	203 participants
BASELINE PD-L1 EXPRESSION ≥1%		41.9 (35.0 to 49.0)	27.6 (21.6 to 34.3)
BASELINE PD-L1 EXPRESSION < 1%	Number Analyzed	135 participants	129 participants
BASELINE PD-L1 EXPRESSION < 1%		31.1 (23.4 to 39.6)	20.9 (14.3 to 29.0)
Non-Quantifiable PD-L1 Expression	Number Analyzed	21 participants	25 participants
Non-Quantifiable PD-L1 Expression		33.3 (14.6 to 57.0)	28.0 (12.1 to 49.4)
BASELINE PD-L1 EXPRESSION 1 - 49%	Number Analyzed	127 participants	106 participants
BASELINE PD-L1 EXPRESSION 1 - 49%		37.8 (29.3 to 46.8)	24.5 (16.7 to 33.8)
BASELINE PD-L1 EXPRESSION >= 50%	Number Analyzed	76 participants	97 participants
BASELINE PD-L1 EXPRESSION >= 50%		48.7 (37.0 to 60.4)	30.9 (21.9 to 41.1)

7.Secondary Outcome


Title	PFS by BICR by PD-L1 Tumor Cell Expression
Description	PFS (primary definition) was defined as the time from the randomizatio...
Description	PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
Time Frame	From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants, Global Population


Arm/Group Title		Treatment A	Treatment B
Arm/Group Description:		Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:		Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed		361	358
Median (95% Confidence Interval) Unit of Measure: Months
< 1% PD-L1 Expression	Number Analyzed	135 participants	129 participants
< 1% PD-L1 Expression		5.82 (4.40 to 7.26)	4.86 (4.17 to 5.65)
>= 1% PD-L1 Expression	Number Analyzed	203 participants	203 participants
>= 1% PD-L1 Expression		7.03 (5.55 to 8.51)	4.70 (4.24 to 5.55)
with 1-49% PD-L1 Expression	Number Analyzed	127 participants	106 participants
with 1-49% PD-L1 Expression		6.74 (5.39 to 8.51)	5.29 (4.24 to 5.68)
with >= 50% PD-L1 Expression	Number Analyzed	76 participants	97 participants
with >= 50% PD-L1 Expression		8.28 (4.47 to 11.50)	4.27 (4.14 to 5.45)
Non-Quantifiable PD-L1 Expression	Number Analyzed	21 participants	25 participants
Non-Quantifiable PD-L1 Expression		6.14 (3.61 to 11.47)	5.78 (2.83 to 8.84)

8.Secondary Outcome


Title	OS by PD-L1 Tumor Cell Expression
Description	OS was defined as the time from randomization to the date of death fro...
Description	OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
Time Frame	From date of randomization to date of death (assessed up to October 2019, approximately 23 months)

Outcome Measure Data

Analysis Population Description

All Randomized Participants, Global Population


Arm/Group Title		Treatment A	Treatment B
Arm/Group Description:		Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description:		Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
Overall Number of Participants Analyzed		361	358
Median (95% Confidence Interval) Unit of Measure: Months
< 1% PD-L1 Expression	Number Analyzed	135 participants	129 participants
< 1% PD-L1 Expression		14.03 ^[1] (13.24 to NA)	9.95 (7.69 to 13.73)
>= 1% PD-L1 Expression	Number Analyzed	203 participants	203 participants
>= 1% PD-L1 Expression		14.23 ^[1] (13.08 to NA)	10.58 (9.36 to 12.55)
with 1-49% PD-L1 Expression	Number Analyzed	127 participants	106 participants
with 1-49% PD-L1 Expression		14.46 ^[1] (12.45 to NA)	10.25 (8.67 to 12.22)
with >= 50% PD-L1 Expression	Number Analyzed	76 participants	97 participants
with >= 50% PD-L1 Expression		14.13 ^[1] (12.39 to NA)	11.86 ^[1] (9.26 to NA)
Non-Quantifiable PD-L1 Expression	Number Analyzed	21 participants	25 participants
Non-Quantifiable PD-L1 Expression		10.84 (7.16 to 15.57)	17.05 ^[1] (8.64 to NA)

[1]

Upper Limit Not Reached

Adverse Events

Time Frame	30 days after last dose, assessed up to October 2019, approximately 23 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Nivolumab + Ipilimumab + Chemothera...	Chemotherapy only
Arm/Group Description	Nivolumab + Ipilimumab + Chemotherapy	Chemotherapy only
All-Cause Mortality
	Treatment A	Treatment B
	Affected / at Risk (%)	Affected / at Risk (%)
Total	153/358 (42.74%)	191/349 (54.73%)
Serious Adverse Events Serious Adverse Events
	Treatment A	Treatment B
	Affected / at Risk (%)	Affected / at Risk (%)
Total	203/358 (56.70%)	144/349 (41.26%)
Blood and lymphatic system disorders
Anaemia ^† 1	11/358 (3.07%)	14/349 (4.01%)
Febrile bone marrow aplasia ^† 1	1/358 (0.28%)	1/349 (0.29%)
Febrile neutropenia ^† 1	11/358 (3.07%)	9/349 (2.58%)
Neutropenia ^† 1	4/358 (1.12%)	4/349 (1.15%)
Pancytopenia ^† 1	1/358 (0.28%)	5/349 (1.43%)
Thrombocytopenia ^† 1	3/358 (0.84%)	7/349 (2.01%)
Cardiac disorders
Acute coronary syndrome ^† 1	0/358 (0.00%)	1/349 (0.29%)
Acute myocardial infarction ^† 1	2/358 (0.56%)	0/349 (0.00%)
Angina pectoris ^† 1	1/358 (0.28%)	0/349 (0.00%)
Atrial fibrillation ^† 1	2/358 (0.56%)	2/349 (0.57%)
Cardiac failure ^† 1	2/358 (0.56%)	1/349 (0.29%)
Cardiac failure congestive ^† 1	1/358 (0.28%)	0/349 (0.00%)
Cardio-respiratory arrest ^† 1	1/358 (0.28%)	1/349 (0.29%)
Cardiovascular insufficiency ^† 1	0/358 (0.00%)	1/349 (0.29%)
Myocardial infarction ^† 1	2/358 (0.56%)	0/349 (0.00%)
Sinus bradycardia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Sinus tachycardia ^† 1	0/358 (0.00%)	1/349 (0.29%)
Ventricular dysfunction ^† 1	1/358 (0.28%)	0/349 (0.00%)
Ear and labyrinth disorders
Deafness ^† 1	1/358 (0.28%)	0/349 (0.00%)
Endocrine disorders
Adrenal insufficiency ^† 1	6/358 (1.68%)	0/349 (0.00%)
Endocrine disorder ^† 1	1/358 (0.28%)	0/349 (0.00%)
Hypophysitis ^† 1	3/358 (0.84%)	0/349 (0.00%)
Hypothalamo-pituitary disorder ^† 1	1/358 (0.28%)	0/349 (0.00%)
Lymphocytic hypophysitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Eye disorders
Cataract ^† 1	1/358 (0.28%)	0/349 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	1/358 (0.28%)	1/349 (0.29%)
Abdominal pain upper ^† 1	0/358 (0.00%)	1/349 (0.29%)
Anal haemorrhage ^† 1	1/358 (0.28%)	0/349 (0.00%)
Autoimmune pancreatitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Colitis ^† 1	5/358 (1.40%)	0/349 (0.00%)
Colitis ulcerative ^† 1	1/358 (0.28%)	0/349 (0.00%)
Constipation ^† 1	0/358 (0.00%)	1/349 (0.29%)
Diarrhoea ^† 1	13/358 (3.63%)	2/349 (0.57%)
Duodenitis ^† 1	0/358 (0.00%)	1/349 (0.29%)
Dysphagia ^† 1	1/358 (0.28%)	2/349 (0.57%)
Enterocolitis ^† 1	0/358 (0.00%)	1/349 (0.29%)
Faecaloma ^† 1	0/358 (0.00%)	1/349 (0.29%)
Food poisoning ^† 1	0/358 (0.00%)	1/349 (0.29%)
Gastric ulcer haemorrhage ^† 1	1/358 (0.28%)	0/349 (0.00%)
Haemorrhoids ^† 1	0/358 (0.00%)	1/349 (0.29%)
Incarcerated inguinal hernia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Inguinal hernia ^† 1	0/358 (0.00%)	1/349 (0.29%)
Large intestinal obstruction ^† 1	0/358 (0.00%)	1/349 (0.29%)
Nausea ^† 1	5/358 (1.40%)	3/349 (0.86%)
Pancreatitis ^† 1	3/358 (0.84%)	0/349 (0.00%)
Rectal haemorrhage ^† 1	0/358 (0.00%)	1/349 (0.29%)
Rectal obstruction ^† 1	0/358 (0.00%)	1/349 (0.29%)
Stomatitis ^† 1	1/358 (0.28%)	1/349 (0.29%)
Upper gastrointestinal haemorrhage ^† 1	1/358 (0.28%)	0/349 (0.00%)
Vomiting ^† 1	6/358 (1.68%)	4/349 (1.15%)
General disorders
Asthenia ^† 1	3/358 (0.84%)	2/349 (0.57%)
Death ^† 1	1/358 (0.28%)	0/349 (0.00%)
Fatigue ^† 1	2/358 (0.56%)	0/349 (0.00%)
General physical health deterioration ^† 1	5/358 (1.40%)	3/349 (0.86%)
Inflammation ^† 1	1/358 (0.28%)	0/349 (0.00%)
Influenza like illness ^† 1	1/358 (0.28%)	0/349 (0.00%)
Mucosal inflammation ^† 1	1/358 (0.28%)	1/349 (0.29%)
Non-cardiac chest pain ^† 1	0/358 (0.00%)	1/349 (0.29%)
Oedema peripheral ^† 1	4/358 (1.12%)	0/349 (0.00%)
Pain ^† 1	0/358 (0.00%)	3/349 (0.86%)
Polyserositis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pyrexia ^† 1	4/358 (1.12%)	1/349 (0.29%)
Sudden death ^† 1	1/358 (0.28%)	1/349 (0.29%)
Hepatobiliary disorders
Autoimmune hepatitis ^† 1	2/358 (0.56%)	0/349 (0.00%)
Cholestasis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Drug-induced liver injury ^† 1	1/358 (0.28%)	0/349 (0.00%)
Hepatic function abnormal ^† 1	1/358 (0.28%)	0/349 (0.00%)
Hepatitis ^† 1	3/358 (0.84%)	0/349 (0.00%)
Hepatocellular injury ^† 1	3/358 (0.84%)	0/349 (0.00%)
Hepatotoxicity ^† 1	1/358 (0.28%)	0/349 (0.00%)
Hydrocholecystis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Immune system disorders
Contrast media reaction ^† 1	1/358 (0.28%)	0/349 (0.00%)
Drug hypersensitivity ^† 1	2/358 (0.56%)	1/349 (0.29%)
Infections and infestations
Abdominal infection ^† 1	1/358 (0.28%)	0/349 (0.00%)
Abscess jaw ^† 1	0/358 (0.00%)	1/349 (0.29%)
Appendicitis ^† 1	2/358 (0.56%)	1/349 (0.29%)
Bronchitis ^† 1	6/358 (1.68%)	0/349 (0.00%)
Cellulitis ^† 1	0/358 (0.00%)	3/349 (0.86%)
Device related infection ^† 1	1/358 (0.28%)	0/349 (0.00%)
Empyema ^† 1	1/358 (0.28%)	0/349 (0.00%)
Escherichia infection ^† 1	0/358 (0.00%)	1/349 (0.29%)
Gastroenteritis viral ^† 1	1/358 (0.28%)	0/349 (0.00%)
Herpes zoster ^† 1	0/358 (0.00%)	1/349 (0.29%)
Infective spondylitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Localised infection ^† 1	1/358 (0.28%)	0/349 (0.00%)
Lower respiratory tract infection ^† 1	1/358 (0.28%)	1/349 (0.29%)
Lung abscess ^† 1	1/358 (0.28%)	1/349 (0.29%)
Lung infection ^† 1	3/358 (0.84%)	0/349 (0.00%)
Neutropenic sepsis ^† 1	2/358 (0.56%)	0/349 (0.00%)
Osteomyelitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Peritonitis ^† 1	0/358 (0.00%)	1/349 (0.29%)
Pneumonia ^† 1	16/358 (4.47%)	16/349 (4.58%)
Pneumonia bacterial ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pulmonary mycosis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pulmonary sepsis ^† 1	1/358 (0.28%)	2/349 (0.57%)
Pulmonary tuberculosis ^† 1	0/358 (0.00%)	1/349 (0.29%)
Pyelonephritis ^† 1	1/358 (0.28%)	1/349 (0.29%)
Respiratory tract infection ^† 1	3/358 (0.84%)	3/349 (0.86%)
Sepsis ^† 1	3/358 (0.84%)	2/349 (0.57%)
Septic shock ^† 1	0/358 (0.00%)	2/349 (0.57%)
Tooth infection ^† 1	0/358 (0.00%)	1/349 (0.29%)
Tuberculosis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Urethritis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Urinary tract infection ^† 1	1/358 (0.28%)	2/349 (0.57%)
Injury, poisoning and procedural complications
Facial bones fracture ^† 1	0/358 (0.00%)	1/349 (0.29%)
Fall ^† 1	1/358 (0.28%)	0/349 (0.00%)
Femoral neck fracture ^† 1	1/358 (0.28%)	0/349 (0.00%)
Femur fracture ^† 1	2/358 (0.56%)	0/349 (0.00%)
Infusion related reaction ^† 1	2/358 (0.56%)	0/349 (0.00%)
Toxicity to various agents ^† 1	0/358 (0.00%)	1/349 (0.29%)
Investigations
Alanine aminotransferase increased ^† 1	2/358 (0.56%)	0/349 (0.00%)
Aspartate aminotransferase increased ^† 1	1/358 (0.28%)	0/349 (0.00%)
Blood alkaline phosphatase increased ^† 1	1/358 (0.28%)	0/349 (0.00%)
Blood creatinine increased ^† 1	1/358 (0.28%)	0/349 (0.00%)
C-reactive protein increased ^† 1	2/358 (0.56%)	0/349 (0.00%)
Haematocrit decreased ^† 1	0/358 (0.00%)	1/349 (0.29%)
Neutrophil count decreased ^† 1	0/358 (0.00%)	2/349 (0.57%)
Transaminases increased ^† 1	2/358 (0.56%)	0/349 (0.00%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	1/358 (0.28%)	3/349 (0.86%)
Dehydration ^† 1	5/358 (1.40%)	4/349 (1.15%)
Diabetes mellitus ^† 1	1/358 (0.28%)	0/349 (0.00%)
Electrolyte imbalance ^† 1	0/358 (0.00%)	1/349 (0.29%)
Hypercalcaemia ^† 1	2/358 (0.56%)	1/349 (0.29%)
Hypoglycaemia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Hypokalaemia ^† 1	0/358 (0.00%)	1/349 (0.29%)
Hyponatraemia ^† 1	2/358 (0.56%)	1/349 (0.29%)
Type 2 diabetes mellitus ^† 1	1/358 (0.28%)	0/349 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Arthritis ^† 1	3/358 (0.84%)	1/349 (0.29%)
Back pain ^† 1	1/358 (0.28%)	0/349 (0.00%)
Bone pain ^† 1	1/358 (0.28%)	0/349 (0.00%)
Fistula ^† 1	0/358 (0.00%)	1/349 (0.29%)
Hypercreatinaemia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Muscular weakness ^† 1	1/358 (0.28%)	0/349 (0.00%)
Musculoskeletal chest pain ^† 1	1/358 (0.28%)	0/349 (0.00%)
Musculoskeletal pain ^† 1	1/358 (0.28%)	0/349 (0.00%)
Myalgia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Neck pain ^† 1	1/358 (0.28%)	0/349 (0.00%)
Osteitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pain in extremity ^† 1	1/358 (0.28%)	1/349 (0.29%)
Spinal pain ^† 1	0/358 (0.00%)	1/349 (0.29%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal neoplasm ^† 1	1/358 (0.28%)	0/349 (0.00%)
Lung neoplasm malignant ^† 1	1/358 (0.28%)	0/349 (0.00%)
Lymphangiosis carcinomatosa ^† 1	1/358 (0.28%)	0/349 (0.00%)
Malignant neoplasm progression ^† 1	28/358 (7.82%)	29/349 (8.31%)
Metastases to bone ^† 1	1/358 (0.28%)	0/349 (0.00%)
Metastases to kidney ^† 1	0/358 (0.00%)	1/349 (0.29%)
Metastases to meninges ^† 1	0/358 (0.00%)	1/349 (0.29%)
Neoplasm ^† 1	1/358 (0.28%)	0/349 (0.00%)
Non-small cell lung cancer ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pericardial effusion malignant ^† 1	1/358 (0.28%)	0/349 (0.00%)
Squamous cell carcinoma ^† 1	1/358 (0.28%)	0/349 (0.00%)
Transitional cell carcinoma ^† 1	1/358 (0.28%)	0/349 (0.00%)
Tumour associated fever ^† 1	1/358 (0.28%)	0/349 (0.00%)
Nervous system disorders
Agraphia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Brain oedema ^† 1	1/358 (0.28%)	0/349 (0.00%)
Cerebral infarction ^† 1	1/358 (0.28%)	0/349 (0.00%)
Cerebrovascular accident ^† 1	0/358 (0.00%)	2/349 (0.57%)
Depressed level of consciousness ^† 1	1/358 (0.28%)	0/349 (0.00%)
Dizziness ^† 1	1/358 (0.28%)	0/349 (0.00%)
Encephalitis autoimmune ^† 1	1/358 (0.28%)	0/349 (0.00%)
Epilepsy ^† 1	0/358 (0.00%)	2/349 (0.57%)
Generalised tonic-clonic seizure ^† 1	1/358 (0.28%)	0/349 (0.00%)
Headache ^† 1	3/358 (0.84%)	0/349 (0.00%)
Hemiparesis ^† 1	0/358 (0.00%)	1/349 (0.29%)
Motor dysfunction ^† 1	1/358 (0.28%)	0/349 (0.00%)
Nervous system disorder ^† 1	1/358 (0.28%)	0/349 (0.00%)
Neuropathy peripheral ^† 1	0/358 (0.00%)	1/349 (0.29%)
Paraesthesia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Seizure ^† 1	2/358 (0.56%)	1/349 (0.29%)
Spinal cord compression ^† 1	0/358 (0.00%)	1/349 (0.29%)
Transient ischaemic attack ^† 1	2/358 (0.56%)	1/349 (0.29%)
Psychiatric disorders
Anxiety ^† 1	1/358 (0.28%)	0/349 (0.00%)
Confusional state ^† 1	2/358 (0.56%)	1/349 (0.29%)
Mental status changes ^† 1	0/358 (0.00%)	1/349 (0.29%)
Renal and urinary disorders
Acute kidney injury ^† 1	8/358 (2.23%)	5/349 (1.43%)
Autoimmune nephritis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Haematuria ^† 1	0/358 (0.00%)	1/349 (0.29%)
Renal colic ^† 1	0/358 (0.00%)	1/349 (0.29%)
Renal failure ^† 1	3/358 (0.84%)	1/349 (0.29%)
Urinary retention ^† 1	1/358 (0.28%)	2/349 (0.57%)
Reproductive system and breast disorders
Acquired hydrocele ^† 1	0/358 (0.00%)	1/349 (0.29%)
Balanoposthitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pelvic pain ^† 1	1/358 (0.28%)	0/349 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	2/358 (0.56%)	2/349 (0.57%)
Chronic obstructive pulmonary disease ^† 1	2/358 (0.56%)	2/349 (0.57%)
Dyspnoea ^† 1	8/358 (2.23%)	7/349 (2.01%)
Epistaxis ^† 1	0/358 (0.00%)	1/349 (0.29%)
Haemoptysis ^† 1	3/358 (0.84%)	3/349 (0.86%)
Hypoxia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Immune-mediated pneumonitis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Interstitial lung disease ^† 1	0/358 (0.00%)	1/349 (0.29%)
Pleural effusion ^† 1	4/358 (1.12%)	1/349 (0.29%)
Pleuritic pain ^† 1	1/358 (0.28%)	1/349 (0.29%)
Pneumonia aspiration ^† 1	1/358 (0.28%)	1/349 (0.29%)
Pneumonitis ^† 1	7/358 (1.96%)	4/349 (1.15%)
Pneumothorax ^† 1	1/358 (0.28%)	0/349 (0.00%)
Pulmonary embolism ^† 1	4/358 (1.12%)	3/349 (0.86%)
Pulmonary haemorrhage ^† 1	1/358 (0.28%)	0/349 (0.00%)
Respiratory failure ^† 1	7/358 (1.96%)	1/349 (0.29%)
Skin and subcutaneous tissue disorders
Rash ^† 1	2/358 (0.56%)	0/349 (0.00%)
Rash maculo-papular ^† 1	2/358 (0.56%)	0/349 (0.00%)
Skin toxicity ^† 1	1/358 (0.28%)	0/349 (0.00%)
Stevens-Johnson syndrome ^† 1	2/358 (0.56%)	0/349 (0.00%)
Vascular disorders
Arterial occlusive disease ^† 1	0/358 (0.00%)	2/349 (0.57%)
Deep vein thrombosis ^† 1	1/358 (0.28%)	0/349 (0.00%)
Embolism ^† 1	0/358 (0.00%)	1/349 (0.29%)
Hypertension ^† 1	0/358 (0.00%)	1/349 (0.29%)
Peripheral ischaemia ^† 1	1/358 (0.28%)	0/349 (0.00%)
Superior vena cava syndrome ^† 1	2/358 (0.56%)	0/349 (0.00%)
Thrombosis ^† 1	2/358 (0.56%)	1/349 (0.29%)
Venous thrombosis ^† 1	1/358 (0.28%)	0/349 (0.00%)
1 Term from vocabulary, MedDRA 22.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment A	Treatment B
	Affected / at Risk (%)	Affected / at Risk (%)
Total	336/358 (93.85%)	322/349 (92.26%)
Blood and lymphatic system disorders
Anaemia ^† 1	111/358 (31.01%)	156/349 (44.70%)
Neutropenia ^† 1	34/358 (9.50%)	59/349 (16.91%)
Thrombocytopenia ^† 1	18/358 (5.03%)	34/349 (9.74%)
Endocrine disorders
Hyperthyroidism ^† 1	29/358 (8.10%)	2/349 (0.57%)
Hypothyroidism ^† 1	55/358 (15.36%)	11/349 (3.15%)
Gastrointestinal disorders
Abdominal pain ^† 1	23/358 (6.42%)	21/349 (6.02%)
Abdominal pain upper ^† 1	18/358 (5.03%)	15/349 (4.30%)
Constipation ^† 1	76/358 (21.23%)	78/349 (22.35%)
Diarrhoea ^† 1	98/358 (27.37%)	63/349 (18.05%)
Nausea ^† 1	111/358 (31.01%)	143/349 (40.97%)
Vomiting ^† 1	60/358 (16.76%)	59/349 (16.91%)
General disorders
Asthenia ^† 1	102/358 (28.49%)	86/349 (24.64%)
Fatigue ^† 1	76/358 (21.23%)	55/349 (15.76%)
Mucosal inflammation ^† 1	19/358 (5.31%)	10/349 (2.87%)
Oedema peripheral ^† 1	24/358 (6.70%)	27/349 (7.74%)
Pyrexia ^† 1	46/358 (12.85%)	34/349 (9.74%)
Investigations
Alanine aminotransferase increased ^† 1	27/358 (7.54%)	17/349 (4.87%)
Amylase increased ^† 1	27/358 (7.54%)	9/349 (2.58%)
Aspartate aminotransferase increased ^† 1	22/358 (6.15%)	11/349 (3.15%)
Blood alkaline phosphatase increased ^† 1	19/358 (5.31%)	18/349 (5.16%)
Blood creatinine increased ^† 1	21/358 (5.87%)	20/349 (5.73%)
Lipase increased ^† 1	27/358 (7.54%)	5/349 (1.43%)
Weight decreased ^† 1	32/358 (8.94%)	21/349 (6.02%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	101/358 (28.21%)	75/349 (21.49%)
Dehydration ^† 1	18/358 (5.03%)	6/349 (1.72%)
Hyperglycaemia ^† 1	24/358 (6.70%)	24/349 (6.88%)
Hypoalbuminaemia ^† 1	20/358 (5.59%)	20/349 (5.73%)
Hypomagnesaemia ^† 1	22/358 (6.15%)	24/349 (6.88%)
Hyponatraemia ^† 1	30/358 (8.38%)	18/349 (5.16%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	47/358 (13.13%)	25/349 (7.16%)
Back pain ^† 1	43/358 (12.01%)	30/349 (8.60%)
Myalgia ^† 1	29/358 (8.10%)	13/349 (3.72%)
Pain in extremity ^† 1	25/358 (6.98%)	13/349 (3.72%)
Nervous system disorders
Dizziness ^† 1	27/358 (7.54%)	16/349 (4.58%)
Headache ^† 1	38/358 (10.61%)	25/349 (7.16%)
Psychiatric disorders
Insomnia ^† 1	22/358 (6.15%)	12/349 (3.44%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	55/358 (15.36%)	39/349 (11.17%)
Dyspnoea ^† 1	54/358 (15.08%)	40/349 (11.46%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	41/358 (11.45%)	34/349 (9.74%)
Dry skin ^† 1	19/358 (5.31%)	3/349 (0.86%)
Pruritus ^† 1	72/358 (20.11%)	8/349 (2.29%)
Rash ^† 1	66/358 (18.44%)	14/349 (4.01%)
Rash maculo-papular ^† 1	19/358 (5.31%)	5/349 (1.43%)
1 Term from vocabulary, MedDRA 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

Layout table for Results Point of Contact information

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):

Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, Richardet E, Bennouna J, Felip E, Juan-Vidal O, Alexandru A, Sakai H, Lingua A, Salman P, Souquet PJ, De Marchi P, Martin C, Perol M, Scherpereel A, Lu S, John T, Carbone DP, Meadows-Shropshire S, Agrawal S, Oukessou A, Yan J, Reck M. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198-211. doi: 10.1016/S1470-2045(20)30641-0. Epub 2021 Jan 18. Erratum In: Lancet Oncol. 2021 Mar;22(3):e92.

Layout table for additonal information

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT03215706
Other Study ID Numbers:	CA209-9LA 2017-001195-35 ( EudraCT Number )
First Submitted:	July 11, 2017
First Posted:	July 12, 2017
Results First Submitted:	August 15, 2020
Results First Posted:	September 16, 2020
Last Update Posted:	January 10, 2024

To Top