A Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC) (CheckMate 816)

• ClinicalTrials.gov Identifier: NCT02998528
• Recruitment Status: Active, not recruiting
• First Posted: December 20, 2016
• Results First Posted: September 28, 2022
• Last Update Posted: October 16, 2023
• Sponsor: Bristol-Myers Squibb
• 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: Non Small Cell Lung Cancer
• Interventions: Biological: Nivolumab; Drug: Cisplatin; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Docetaxel; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Biological: Ipilimumab
• Enrollment: 505

Participant Flow

Recruitment Details

Pre-assignment Details

One participant randomized to Arm A (nivo+ipi) received the wrong treatment of chemo. This participant is counted in Arm A for baseline and efficacy analyses (analyses based on the randomized population) and is counted in Arm B (chemo) for exposure and safety analyses (based on the treated population). This participant was randomized prior to Revised Protocol 02 and is not included in the All Treated Participants from the Concurrently Randomized Arms B and C population.

Arm/Group Title	Arm A: Nivo 3 mg/kg + Ipi 1 mg/kg	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
Arm/Group Description	Participants received nivolumab 3 mg/kg IV over 30 minutes every 2 weeks for up to 3 doses (ie, 6 weeks of treatment; each cycle is 14 days). In Cycle 1 Day 1 only, nivolumab will be followed by a single dose of ipilimumab 1 mg/kg IV over 30 minutes. Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.
Period Title: Randomization Period
Started	113	213	179
All Concurrently Randomized Participants in Arms B and C [1]	0	179	179
Completed	112	207	176
Not Completed	1	6	3
Reason Not Completed
Adverse event unrelated to study drug	0	0	1
Participant withdrew consent	0	3	0
Participant no longer meets study criteria	1	3	2
[1] The primary population for efficacy analyses
Period Title: Neoadjuvant Treatment Period
Started	111	208	176
All Treated Participants From Concurrently Randomized Arms B and C [1]	0	176	176
Completed	101	177	165
Not Completed	10	31	11
Reason Not Completed
Participant request to discontinue study treatment	0	7	0
Participant withdrew consent	0	4	0
Participant no longer meets study criteria	0	1	0
Disease progression	3	2	1
Study drug toxicity	6	14	10
Death	1	0	0
Adverse event unrelated to study treatment	0	3	0
[1] The primary population for safety analyses
Period Title: Systemic Adjuvant Treatment Period
Started	37	47	26
Completed	28	41	22
Not Completed	9	6	4
Reason Not Completed
Disease progression	1	0	0
Study drug toxicity	4	5	1
Adverse event unrelated to study drug	1	0	1
Participant request to discontinue treatment	3	1	1
Other reasons	0	0	1

Baseline Characteristics

Arm/Group Title		Arm A: Nivo 3 mg/kg + Ipi 1 mg/kg	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo	Total
Arm/Group Description		Participants received nivolumab 3 mg/kg IV over 30 minutes every 2 weeks for up to 3 doses (ie, 6 weeks of treatment; each cycle is 14 days). In Cycle 1 Day 1 only, nivolumab will be followed by a single dose of ipilimumab 1 mg/kg IV over 30 minutes. Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Total of all reporting groups
Overall Number of Baseline Participants		113	213	179	505
Baseline Analysis Population Description		All randomized participants
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	113 participants	213 participants	179 participants	505 participants
< 65		62	99	93	254
>= 65 AND < 75		40	96	75	211
>= 75 AND < 85		11	17	11	39
>= 85		0	1	0	1
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	213 participants	179 participants	505 participants
	Female	40 35.4%	65 30.5%	51 28.5%	156 30.9%
	Male	73 64.6%	148 69.5%	128 71.5%	349 69.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	213 participants	179 participants	505 participants
	Hispanic or Latino	2 1.8%	5 2.3%	0 0.0%	7 1.4%
	Not Hispanic or Latino	53 46.9%	105 49.3%	100 55.9%	258 51.1%
	Unknown or Not Reported	58 51.3%	103 48.4%	79 44.1%	240 47.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	213 participants	179 participants	505 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	41 36.3%	96 45.1%	86 48.0%	223 44.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 3.5%	5 2.3%	4 2.2%	13 2.6%
	White	64 56.6%	108 50.7%	89 49.7%	261 51.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	4 3.5%	4 1.9%	0 0.0%	8 1.6%

Outcome Measures

1. Primary Outcome

Title	Event-Free Survival (EFS)
Description	Event-free survival (EFS) is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on blinded independent central review (BICR) assessment per response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time Frame	From randomization to disease progression, reoccurrence, or death due to any cause. (Up to a median of 30 months)

Outcome Measure Data

Analysis Population Description

All concurrently randomized participants in Arm C and Arm B

Arm/Group Title	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
Arm/Group Description:	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.
Overall Number of Participants Analyzed	179	179
Median (95% Confidence Interval); Unit of Measure: Months
	20.80; (14.03 to 26.71)	31.57 [1]; (30.16 to NA)

[1]

Insufficient number of participants with events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B: Platinum Doublet Chemo, Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0052
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified by PD-L1 (≥ 1% vs <1%/unevaluable/indeterminate), disease stage (IB/II vs IIIA), and sex (male vs female)
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 97.38%; 0.43 to 0.91
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Pathologic Complete Response (pCR) Rate
Description	Pathologic complete response (pCR) rate is defined as the number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR).
Time Frame	From randomization up to a median of 30 months after randomization.

Outcome Measure Data

Analysis Population Description

All concurrently randomized participants in Arm C and Arm B

Arm/Group Title	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
Arm/Group Description:	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.
Overall Number of Participants Analyzed	179	179
Measure Type: Count of Participants; Unit of Measure: Participants
	4 2.2%	43 24.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B: Platinum Doublet Chemo, Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	% Difference
	Estimated Value	21.6
	Confidence Interval	(2-Sided) 99%; 13.0 to 30.3
	Estimation Comments	Strata adjusted difference (Arm C - Concurrent Arm B) based on the CMH method of weighting. Stratified by PD-L1 (≥ 1% vs <1%/unevaluable/indeterminate), disease stage (IB/II vs IIIA), and sex (male vs female)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B: Platinum Doublet Chemo, Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	13.94
	Confidence Interval	(2-Sided) 99%; 3.49 to 55.75
	Estimation Comments	Strata adjusted odds ratio (Arm C over Concurrent Arm B) the Mantel-Haenszel method. Stratified by PD-L1 (≥ 1% vs <1%/unevaluable/indeterminate), disease stage (IB/II vs IIIA), and sex (male vs female)

3. Secondary Outcome

Title	Major Pathologic Response (MPR) Rate
Description	Major pathologic response (MPR) rate is defined as number of randomized participants with </= 10% residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.
Time Frame	From randomization up to a median of 30 months after randomization.

Outcome Measure Data

Analysis Population Description

All concurrently randomized participants in Arm C and Arm B

Arm/Group Title	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
Arm/Group Description:	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.
Overall Number of Participants Analyzed	179	179
Measure Type: Count of Participants; Unit of Measure: Participants
	16 8.9%	66 36.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B: Platinum Doublet Chemo, Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	% Difference
	Estimated Value	27.9
	Confidence Interval	(2-Sided) 95%; 19.6 to 36.1
	Estimation Comments	Strata adjusted difference (Arm C - Concurrent Arm B) based on the CMH method of weighting. Stratified by PD-L1 (≥ 1% vs <1%/unevaluable/indeterminate), disease stage (IB/II vs IIIA), and sex (male vs female)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B: Platinum Doublet Chemo, Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.70
	Confidence Interval	(2-Sided) 95%; 3.16 to 10.26
	Estimation Comments	Stratified by PD-L1 (≥ 1% vs <1%/unevaluable/indeterminate), disease stage (IB/II vs IIIA), and sex (male vs female)

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) is defined as the time between the date of randomization and the date of death. OS will be censored on the last date a participant was known to be alive.
Time Frame	From randomization to the date of death

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Time to Death or Distant Metastases (TTDM)
Description	TTDM is defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the thorax using blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Patients who have not developed distant metastasis or died at the time of analysis will be censored on the date of their last evaluable tumor assessment.
Time Frame	From randomization to the first date of distant metastasis or the date of death in the absence of distant metastasis (Up to a median of 30 months)

Outcome Measure Data

Analysis Population Description

All concurrently randomized participants in Arm C and Arm B

Arm/Group Title	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
Arm/Group Description:	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.
Overall Number of Participants Analyzed	179	179
Median (95% Confidence Interval); Unit of Measure: Months
	26.71 [1]; (22.41 to NA)	NA [1]; (36.60 to NA)

[1]

Insufficient number of participants with events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B: Platinum Doublet Chemo, Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.36 to 0.77
	Estimation Comments	Stratified by: PD-L1 status (≥ 1% vs <1%/not evaluable/indeterminate), disease stage (IB/II vs IIIA), and sex (male vs female)

Adverse Events

Time Frame	All-cause mortality was assessed from first dose to primary completion (up to approximately 54 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose of neoadjuvant therapy (up to approximately 5.5 months).
Adverse Event Reporting Description	The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Arm/Group Title	Arm A: Nivo 3 mg/kg + Ipi 1 mg/kg	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
Arm/Group Description	Participants received nivolumab 3 mg/kg IV over 30 minutes every 2 weeks for up to 3 doses (ie, 6 weeks of treatment; each cycle is 14 days). In Cycle 1 Day 1 only, nivolumab will be followed by a single dose of ipilimumab 1 mg/kg IV over 30 minutes. Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive investigator-choice of platinum doublet chemotherapy regimens in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.	Participants receive nivolumab 360 mg IV + platinum doublet chemotherapy in 3-week cycles up to a maximum of 3 cycles of IV chemotherapy (ie, 9 weeks of treatment; each cycle is 21 days). Following definitive surgery, participants could receive up to 4 cycles of adjuvant chemotherapy and/or radiation at the discretion of the investigator.
All-Cause Mortality
	Arm A: Nivo 3 mg/kg + Ipi 1 mg/kg	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	30/113 (26.55%)	76/213 (35.68%)	35/179 (19.55%)
Serious Adverse Events
	Arm A: Nivo 3 mg/kg + Ipi 1 mg/kg	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	30/111 (27.03%)	58/208 (27.88%)	52/176 (29.55%)
Blood and lymphatic system disorders
Anaemia † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Coagulopathy † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Febrile neutropenia † 1	0/111 (0.00%)	6/208 (2.88%)	3/176 (1.70%)
Myelosuppression † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Neutropenia † 1	0/111 (0.00%)	2/208 (0.96%)	0/176 (0.00%)
Pancytopenia † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Sickle cell anaemia with crisis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Thrombocytopenia † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Cardiac disorders
Arteriosclerosis coronary artery † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Atrial fibrillation † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Cardiac failure † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Cardiac ventricular thrombosis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Myocardial infarction † 1	1/111 (0.90%)	1/208 (0.48%)	0/176 (0.00%)
Myocardial ischaemia † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Myocarditis † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Stress cardiomyopathy † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	1/111 (0.90%)	0/208 (0.00%)	1/176 (0.57%)
Hypophysitis † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Inappropriate antidiuretic hormone secretion † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Eye disorders
Ocular myasthenia † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Gastrointestinal disorders
Abdominal pain upper † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Colitis † 1	1/111 (0.90%)	1/208 (0.48%)	0/176 (0.00%)
Constipation † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Diarrhoea † 1	2/111 (1.80%)	2/208 (0.96%)	0/176 (0.00%)
Gastric ulcer † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Haematochezia † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Nausea † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Oesophageal perforation † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Small intestinal obstruction † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Vomiting † 1	0/111 (0.00%)	1/208 (0.48%)	4/176 (2.27%)
General disorders
Death † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
General physical health deterioration † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Malaise † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Hepatobiliary disorders
Drug-induced liver injury † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Hepatitis † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Immune system disorders
Anaphylactic reaction † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Hypersensitivity † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Infections and infestations
Bacteraemia † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Cellulitis † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Empyema † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Enterocolitis infectious † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Gastroenteritis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Infectious pleural effusion † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Influenza † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Klebsiella bacteraemia † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Nasopharyngitis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Pleural infection † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Pneumonia † 1	5/111 (4.50%)	8/208 (3.85%)	6/176 (3.41%)
Pneumonia bacterial † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Pneumonia influenzal † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Post procedural infection † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Pyelonephritis acute † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Respiratory tract infection † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Sepsis † 1	1/111 (0.90%)	0/208 (0.00%)	1/176 (0.57%)
Septic shock † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Subcutaneous abscess † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Tuberculosis † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Upper respiratory tract infection † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Urinary tract infection † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Wound infection † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Injury, poisoning and procedural complications
Cardiac function disturbance postoperative † 1	1/111 (0.90%)	1/208 (0.48%)	0/176 (0.00%)
Overdose † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Post procedural complication † 1	1/111 (0.90%)	1/208 (0.48%)	2/176 (1.14%)
Post procedural haematoma † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Post procedural haemorrhage † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Postoperative delirium † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Postoperative respiratory failure † 1	2/111 (1.80%)	0/208 (0.00%)	0/176 (0.00%)
Postoperative wound complication † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Procedural haemorrhage † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Investigations
Aspartate aminotransferase increased † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Blood creatinine increased † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Glycosylated haemoglobin increased † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Hepatic enzyme abnormal † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Transaminases increased † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Hypoalbuminaemia † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Hypokalaemia † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Hyponatraemia † 1	0/111 (0.00%)	2/208 (0.96%)	0/176 (0.00%)
Musculoskeletal and connective tissue disorders
Myositis † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Endometrial cancer † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Malignant neoplasm progression † 1	2/111 (1.80%)	5/208 (2.40%)	2/176 (1.14%)
Renal cancer † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Tumour pseudoprogression † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Nervous system disorders
Carotid artery stenosis † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Cerebral infarction † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Encephalopathy † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Ischaemic stroke † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Myasthenia gravis † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Neuropathy peripheral † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Posterior reversible encephalopathy syndrome † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Syncope † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Renal and urinary disorders
Acute kidney injury † 1	0/111 (0.00%)	2/208 (0.96%)	3/176 (1.70%)
Reproductive system and breast disorders
Prostatitis † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Bronchopleural fistula † 1	0/111 (0.00%)	2/208 (0.96%)	0/176 (0.00%)
Bronchospasm † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Chronic obstructive pulmonary disease † 1	1/111 (0.90%)	0/208 (0.00%)	1/176 (0.57%)
Chylothorax † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Cough † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Dyspnoea † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Epistaxis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Haemoptysis † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Hypoxia † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Interstitial lung disease † 1	1/111 (0.90%)	0/208 (0.00%)	1/176 (0.57%)
Lung opacity † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Pleural effusion † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Pneumonia aspiration † 1	0/111 (0.00%)	1/208 (0.48%)	1/176 (0.57%)
Pneumonitis † 1	4/111 (3.60%)	1/208 (0.48%)	1/176 (0.57%)
Pneumothorax † 1	1/111 (0.90%)	1/208 (0.48%)	1/176 (0.57%)
Pulmonary embolism † 1	1/111 (0.90%)	1/208 (0.48%)	3/176 (1.70%)
Pulmonary fistula † 1	1/111 (0.90%)	2/208 (0.96%)	1/176 (0.57%)
Pulmonary mass † 1	1/111 (0.90%)	0/208 (0.00%)	0/176 (0.00%)
Respiratory failure † 1	0/111 (0.00%)	1/208 (0.48%)	2/176 (1.14%)
Skin and subcutaneous tissue disorders
Rash † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Vascular disorders
Aortic rupture † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Arterial thrombosis † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Deep vein thrombosis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Embolism † 1	0/111 (0.00%)	1/208 (0.48%)	2/176 (1.14%)
Hypotension † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Iliac artery occlusion † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
Subclavian vein thrombosis † 1	0/111 (0.00%)	1/208 (0.48%)	0/176 (0.00%)
Thrombophlebitis superficial † 1	0/111 (0.00%)	0/208 (0.00%)	1/176 (0.57%)
1 Term from vocabulary, 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A: Nivo 3 mg/kg + Ipi 1 mg/kg	Arm B: Platinum Doublet Chemo	Arm C: Nivo 360 mg + Platinum Doublet Chemo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	102/111 (91.89%)	200/208 (96.15%)	157/176 (89.20%)
Blood and lymphatic system disorders
Anaemia † 1	8/111 (7.21%)	75/208 (36.06%)	62/176 (35.23%)
Leukopenia † 1	0/111 (0.00%)	16/208 (7.69%)	16/176 (9.09%)
Neutropenia † 1	1/111 (0.90%)	38/208 (18.27%)	30/176 (17.05%)
Thrombocytopenia † 1	0/111 (0.00%)	17/208 (8.17%)	5/176 (2.84%)
Cardiac disorders
Atrial fibrillation † 1	0/111 (0.00%)	8/208 (3.85%)	9/176 (5.11%)
Ear and labyrinth disorders
Tinnitus † 1	1/111 (0.90%)	17/208 (8.17%)	6/176 (3.41%)
Endocrine disorders
Hyperthyroidism † 1	7/111 (6.31%)	0/208 (0.00%)	7/176 (3.98%)
Hypothyroidism † 1	11/111 (9.91%)	0/208 (0.00%)	2/176 (1.14%)
Gastrointestinal disorders
Constipation † 1	24/111 (21.62%)	72/208 (34.62%)	63/176 (35.80%)
Diarrhoea † 1	18/111 (16.22%)	34/208 (16.35%)	21/176 (11.93%)
Nausea † 1	24/111 (21.62%)	104/208 (50.00%)	73/176 (41.48%)
Stomatitis † 1	4/111 (3.60%)	12/208 (5.77%)	6/176 (3.41%)
Vomiting † 1	10/111 (9.01%)	29/208 (13.94%)	20/176 (11.36%)
General disorders
Asthenia † 1	13/111 (11.71%)	27/208 (12.98%)	19/176 (10.80%)
Fatigue † 1	24/111 (21.62%)	38/208 (18.27%)	30/176 (17.05%)
Malaise † 1	2/111 (1.80%)	27/208 (12.98%)	26/176 (14.77%)
Non-cardiac chest pain † 1	4/111 (3.60%)	12/208 (5.77%)	7/176 (3.98%)
Oedema peripheral † 1	4/111 (3.60%)	11/208 (5.29%)	6/176 (3.41%)
Pain † 1	8/111 (7.21%)	29/208 (13.94%)	17/176 (9.66%)
Pyrexia † 1	18/111 (16.22%)	24/208 (11.54%)	20/176 (11.36%)
Infections and infestations
Pneumonia † 1	3/111 (2.70%)	13/208 (6.25%)	15/176 (8.52%)
Upper respiratory tract infection † 1	4/111 (3.60%)	8/208 (3.85%)	9/176 (5.11%)
Injury, poisoning and procedural complications
Incision site pain † 1	10/111 (9.01%)	6/208 (2.88%)	3/176 (1.70%)
Procedural pain † 1	12/111 (10.81%)	11/208 (5.29%)	13/176 (7.39%)
Wound complication † 1	4/111 (3.60%)	13/208 (6.25%)	13/176 (7.39%)
Investigations
Alanine aminotransferase increased † 1	7/111 (6.31%)	18/208 (8.65%)	13/176 (7.39%)
Aspartate aminotransferase increased † 1	3/111 (2.70%)	14/208 (6.73%)	4/176 (2.27%)
Blood creatinine increased † 1	1/111 (0.90%)	14/208 (6.73%)	15/176 (8.52%)
Neutrophil count decreased † 1	7/111 (6.31%)	44/208 (21.15%)	28/176 (15.91%)
Platelet count decreased † 1	2/111 (1.80%)	13/208 (6.25%)	16/176 (9.09%)
Weight decreased † 1	3/111 (2.70%)	12/208 (5.77%)	9/176 (5.11%)
White blood cell count decreased † 1	4/111 (3.60%)	24/208 (11.54%)	15/176 (8.52%)
Metabolism and nutrition disorders
Decreased appetite † 1	17/111 (15.32%)	53/208 (25.48%)	46/176 (26.14%)
Hyperglycaemia † 1	6/111 (5.41%)	7/208 (3.37%)	5/176 (2.84%)
Hypoalbuminaemia † 1	2/111 (1.80%)	8/208 (3.85%)	10/176 (5.68%)
Hypomagnesaemia † 1	0/111 (0.00%)	18/208 (8.65%)	10/176 (5.68%)
Hyponatraemia † 1	2/111 (1.80%)	16/208 (7.69%)	8/176 (4.55%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	12/111 (10.81%)	13/208 (6.25%)	14/176 (7.95%)
Back pain † 1	6/111 (5.41%)	12/208 (5.77%)	8/176 (4.55%)
Nervous system disorders
Dizziness † 1	10/111 (9.01%)	10/208 (4.81%)	8/176 (4.55%)
Dysgeusia † 1	7/111 (6.31%)	10/208 (4.81%)	4/176 (2.27%)
Headache † 1	9/111 (8.11%)	16/208 (7.69%)	8/176 (4.55%)
Neuropathy peripheral † 1	0/111 (0.00%)	4/208 (1.92%)	10/176 (5.68%)
Psychiatric disorders
Anxiety † 1	8/111 (7.21%)	8/208 (3.85%)	4/176 (2.27%)
Insomnia † 1	8/111 (7.21%)	15/208 (7.21%)	14/176 (7.95%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	15/111 (13.51%)	31/208 (14.90%)	22/176 (12.50%)
Dyspnoea † 1	16/111 (14.41%)	18/208 (8.65%)	14/176 (7.95%)
Hiccups † 1	3/111 (2.70%)	29/208 (13.94%)	18/176 (10.23%)
Skin and subcutaneous tissue disorders
Alopecia † 1	1/111 (0.90%)	28/208 (13.46%)	20/176 (11.36%)
Pruritus † 1	17/111 (15.32%)	7/208 (3.37%)	13/176 (7.39%)
Rash † 1	17/111 (15.32%)	7/208 (3.37%)	25/176 (14.20%)
1 Term from vocabulary, 24.0; † 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.

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

Results Point of Contact

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

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

Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02998528
• Other Study ID Numbers: CA209-816; 2016-003536-21 ( EudraCT Number )
• First Submitted: December 16, 2016
• First Posted: December 20, 2016
• Results First Submitted: August 31, 2022
• Results First Posted: September 28, 2022
• Last Update Posted: October 16, 2023