Trial Outcomes & Findings for A Study of Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Second-Line Nivolumab Monotherapy in Asia (NCT NCT03195491)

NCT ID: NCT03195491

Last Updated: 2024-07-18

Results Overview

Number of non-HBV participants experiencing high grade (combined CTCAE v4 Grade 3-4 and Grade 5) treatment-related select adverse events in non-HBV infected participants. To evaluate safety and tolerability in non-HBV infected participants with advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed during or after one prior systemic therapy and are treated with nivolumab monotherapy with an infusion duration of 30 minutes. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

400 participants

Primary outcome timeframe

From first dose up to 100 days post dose, up to approximately 36 months

Results posted on

2024-07-18

Participant Flow

Participant milestones

Participant milestones
Measure	Non-HBV Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Overall Study STARTED	383	17
Overall Study COMPLETED	36	2
Overall Study NOT COMPLETED	347	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Non-HBV Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Overall Study Study drug toxicity	25	3
Overall Study Maximum clinical benefit	5	0
Overall Study Lost to Follow-up	1	0
Overall Study Death	3	0
Overall Study Adverse event unrelated to study drug	19	2
Overall Study Disease progression	266	8
Overall Study Other reasons	10	0
Overall Study Participant withdrew consent	8	1
Overall Study Participant no longer meets study criteria	0	1
Overall Study Participant request to discontinue study treatment	10	0

Baseline Characteristics

A Study of Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Second-Line Nivolumab Monotherapy in Asia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	Total n=400 Participants Total of all reporting groups
Age, Continuous	60.6 Years STANDARD_DEVIATION 8.72 • n=5 Participants	59.1 Years STANDARD_DEVIATION 7.86 • n=7 Participants	60.5 Years STANDARD_DEVIATION 8.68 • n=5 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	4 Participants n=7 Participants	86 Participants n=5 Participants
Sex: Female, Male Male	301 Participants n=5 Participants	13 Participants n=7 Participants	314 Participants n=5 Participants
Race/Ethnicity, Customized Chinese	377 Participants n=5 Participants	17 Participants n=7 Participants	394 Participants n=5 Participants
Race/Ethnicity, Customized Asian Other	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose up to 100 days post dose, up to approximately 36 months

Population: All treated non-HBV infected participants

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Number of Non-HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Gastrointestinal Adverse	2 Participants	—	—
Number of Non-HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Hepatic Adverse Event	8 Participants	—	—
Number of Non-HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Pulmonary Adverse Event	5 Participants	—	—
Number of Non-HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Renal Adverse Event	2 Participants	—	—
Number of Non-HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Skin Adverse Event	7 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to 100 days post dose, up to approximately 36 months

Population: All treated HBV infected participants

Number of HBV participants experiencing high grade (combined CTCAE v4 Grade 3-4 and Grade 5) treatment-related select adverse events in HBV participants. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=17 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Number of HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Gastrointestinal Adverse Event	0 Participants	—	—
Number of HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Hepatic Adverse Event	0 Participants	—	—
Number of HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Pulmonary Adverse Event	0 Participants	—	—
Number of HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Renal Adverse Event	0 Participants	—	—
Number of HBV Participants Experiencing High Grade Treatment-Related Select Adverse Events Skin Adverse Reaction	1 Participants	—	—

SECONDARY outcome

Timeframe: From first dose up to 100 days post dose, up to approximately 36 months

Population: All treated participants

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Number of Participants Experiencing Adverse Events (AEs)	375 Participants	17 Participants	—

SECONDARY outcome

Timeframe: From the first dose up to the date of death. Participants without documentation of death will be censored on the late date known to be alive, up to approximately 32 months

Population: This is a single arm trial with two enrollment cohorts, HPV positive and HPV negative. All participants received the same treatment. Due to the small number of participants in the HPV cohorts, it is not meaningful to perform additional subgroup analysis. For example, there were only 17 participants in the HPV positive cohort, which is less than 5% (17/400 = 4.25%) from the overall. Therefore, all additional efficacy subgroup analysis was performed based on all treated participants.

Overall survival (OS) is defined as the time from the first dosing date to the date of death. Participants without documentation of death will be recorded on the last date the participant was known to be alive. Tumor PD-L1 protein expression was measured by immunohistochemistry (IHC).

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants n=400 Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Overall Survival (OS) PD-L1 < 5%	—	—	14.65 Months Interval 11.63 to 18.1
Overall Survival (OS) All treated participants	14.16 Months Interval 12.25 to 18.07	22.31 Months Interval 10.02 to Upper limit not calculated due to insufficient number of events.	14.65 Months Interval 12.32 to 18.1
Overall Survival (OS) PD-L1 < 1%	—	—	13.31 Months Interval 10.87 to 17.71
Overall Survival (OS) PD-L1 ≥ 1%	—	—	19.25 Months Interval 12.94 to 23.46
Overall Survival (OS) PD-L1 ≥ 5%	—	—	18.37 Months Interval 11.7 to 22.77
Overall Survival (OS) PD-L1 < 10%	—	—	14.72 Months Interval 12.35 to 18.76
Overall Survival (OS) PD-L1 ≥ 10%	—	—	17.68 Months Interval 10.78 to 21.03
Overall Survival (OS) PD-L1 < 50%	—	—	16.23 Months Interval 12.52 to 18.86
Overall Survival (OS) PD-L1 ≥ 50%	—	—	14.75 Months Interval 10.68 to 29.04
Overall Survival (OS) PD-L1 Not Reportable	—	—	11.99 Months Interval 9.17 to 19.19
Overall Survival (OS) Squamous Tumor Histology	—	—	13.80 Months Interval 10.78 to 18.37
Overall Survival (OS) Non-squamous Tumor Histology	—	—	14.75 Months Interval 11.7 to 19.32
Overall Survival (OS) EGFR Mutation Positive	—	—	19.32 Months Interval 11.24 to 31.74
Overall Survival (OS) ALK translocation positive	—	—	16.48 Months Interval 1.28 to Upper limit not reached due to insufficient number of events.

SECONDARY outcome

Timeframe: From the first dose up to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause, up to approximately 30 months

PFS is the time from first dose to the first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who die without a reported prior progression are considered to have progressed on their death date. Participants who did not progress or die will be documented on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be documented on their first dose date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be documented at the last evaluable tumor assessment prior to initiation of the subsequent anti-cancer therapy. Tumor PD-L1 protein expression was measured by immunohistochemistry (IHC). Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants n=400 Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Progression-Free Survival (PFS) All treated participants	3.61 Months Interval 2.33 to 3.75	2.04 Months Interval 1.64 to 10.22	3.61 Months Interval 2.33 to 3.75
Progression-Free Survival (PFS) PD-L1 < 1%	—	—	2.33 Months Interval 1.94 to 3.68
Progression-Free Survival (PFS) PD-L1 ≥ 1%	—	—	4.73 Months Interval 3.68 to 5.65
Progression-Free Survival (PFS) PD-L1 < 5	—	—	2.37 Months Interval 1.94 to 3.68
Progression-Free Survival (PFS) PD-L1 ≥ 5	—	—	5.42 Months Interval 3.68 to 5.65
Progression-Free Survival (PFS) PD-L1 < 10	—	—	2.50 Months Interval 1.94 to 3.68
Progression-Free Survival (PFS) PD-L1 ≥ 10	—	—	5.45 Months Interval 3.68 to 5.65
Progression-Free Survival (PFS) PD-L1 < 50	—	—	3.58 Months Interval 2.07 to 3.75
Progression-Free Survival (PFS) PD-L1 ≥ 50	—	—	5.55 Months Interval 2.23 to 7.33
Progression-Free Survival (PFS) EGFR mutation positive	—	—	1.87 Months Interval 1.71 to 4.73
Progression-Free Survival (PFS) ALK translocation positive	—	—	1.91 Months Interval 1.28 to 16.36
Progression-Free Survival (PFS) Squamous subgroup	—	—	3.75 Months Interval 3.06 to 5.55
Progression-Free Survival (PFS) Non-squamous subgroup	—	—	2.79 Months Interval 1.94 to 3.68

SECONDARY outcome

Timeframe: From first dose up to 100 days post last dose, up to approximately 36 months

Population: All treated participants

Number of Participants experiencing laboratory abnormalities are defined as on-study lab parameters summarized by using the worst grade per NCI CTCAE v.4 criteria

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 3XULN	16 Participants	1 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 5XULN	5 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 10XULN	4 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 20XULN	2 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests TOTAL BILIRUBIN > 2XULN	4 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY	0 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAY	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From first dose to 100 days post last dose, up to 36 months

Population: All treated participants

Number of Participants experiencing SAEs are tabulated using worst grade per NCI CTCAE v.4 criteria by system organ class and MedDRA preferred term.

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Number of Participants Experiencing Serious Adverse Events (SAEs)	157 Participants	12 Participants	—

SECONDARY outcome

Timeframe: From the first dose date up to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. Up to approximately 36 months

Objective Response Rate (ORR) is defined as the percentage of all treated subjects whose best overall response (BOR) from baseline is either a CR or PR per RECIST 1.1 criteria. BOR is determined by the best response designation recorded between the first dose date and the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For subjects without documented progression or subsequent anticancer therapy, all available response designations will contribute to the BOR determination. For subjects who continue nivolumab beyond progression, the BOR should be determined based on response designations recorded at the time of the initial RECIST 1.1 defined progression.

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants n=400 Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Objective Response Rate All treated participants	14.88 Percentage of participants Interval 11.47 to 18.85	17.65 Percentage of participants Interval 3.8 to 43.43	15.00 Percentage of participants Interval 11.65 to 18.88
Objective Response Rate Squamous tumor histology	—	—	18.38 Percentage of participants Interval 12.26 to 25.93
Objective Response Rate Non-squamous tumor histology	—	—	13.26 Percentage of participants Interval 9.41 to 17.95
Objective Response Rate PD-L1 < 1%	—	—	6.32 Percentage of participants Interval 3.2 to 11.03
Objective Response Rate PD-L1 ≥ 1%	—	—	25.60 Percentage of participants Interval 19.18 to 32.89
Objective Response Rate PD-L1 < 5%	—	—	8.78 Percentage of participants Interval 5.29 to 13.52
Objective Response Rate PD-L1 ≥ 5%	—	—	26.28 Percentage of participants Interval 19.13 to 34.48
Objective Response Rate PD-L1 < 10%	—	—	10.81 Percentage of participants Interval 7.05 to 15.66
Objective Response Rate PD-L1 ≥ 10%	—	—	25.00 Percentage of participants Interval 17.55 to 33.73
Objective Response Rate PD-L1 < 50%	—	—	11.76 Percentage of participants Interval 8.19 to 16.2
Objective Response Rate PD-L1 ≥ 50%	—	—	31.43 Percentage of participants Interval 20.85 to 43.63
Objective Response Rate EGFR mutation positive	—	—	17.65 Percentage of participants Interval 6.76 to 34.53
Objective Response Rate ALK translocation positive	—	—	10.00 Percentage of participants Interval 0.25 to 44.5

SECONDARY outcome

Timeframe: From the date of first confirmed response to the date of the first documented tumor progression, up to approximately 30 months

Duration of Response (DOR) is defined as the time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who neither progress nor die will be documented on the date of their last assessment. The censoring algorithm for DOR will be the same as used for PFS definition. This endpoint will only be evaluated for participants with the best overall response of complete response or partial response.

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=3 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=57 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants n=60 Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Duration of Tumor Response All treated participants	NA Months Interval 8.15 to Median and upper limit not reached due to insufficient number of events.	19.38 Months Interval 11.04 to 24.97	19.38 Months Interval 11.04 to 24.97
Duration of Tumor Response Squamous tumor histology	—	—	12.62 Months Interval 8.11 to 25.33
Duration of Tumor Response Non-squamous tumor histology	—	—	19.61 Months Interval 9.49 to 27.6
Duration of Tumor Response PD-L1 < 1%	—	—	19.38 Months Interval 8.11 to 24.97
Duration of Tumor Response PD-L1 ≥ 1%	—	—	16.11 Months Interval 9.43 to 27.6
Duration of Tumor Response PD-L1 < 5%	—	—	19.38 Months Interval 8.11 to 24.97
Duration of Tumor Response PD-L1 ≥ 5%	—	—	19.61 Months Interval 9.33 to 29.7
Duration of Tumor Response PD-L1 < 10%	—	—	12.06 Months Interval 8.11 to 24.97
Duration of Tumor Response PD-L1 ≥ 10%	—	—	21.13 Months Interval 9.43 to Upper limit not reached due to insufficient number of events.
Duration of Tumor Response PD-L1 < 50%	—	—	12.06 Months Interval 8.15 to 24.97
Duration of Tumor Response PD-L1 ≥ 50%	—	—	21.49 Months Interval 9.3 to Upper limit not reached due to insufficient number of events.
Duration of Tumor Response EGFR mutation positive	—	—	12.57 Months Interval 5.59 to Upper limit not reached due to insufficient number of events.
Duration of Tumor Response ALK translocation positive	—	—	19.42 Months Lower and upper limits not reached due to insufficient number of events.

SECONDARY outcome

Timeframe: From randomization to 100 days post last dose, up to 36 months

Population: All treated participants

Number of participants experiencing laboratory abnormalities are defined as on-study lab parameters summarized by using the worst grade per NCI CTCAE v.4 criteria

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN	87 Participants	1 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN	34 Participants	1 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH TSH <= ULN AT BASELINE	63 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN	36 Participants	1 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN	52 Participants	0 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH FT3/FT4 TEST MISSING	74 Participants	1 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN	66 Participants	3 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH TSH >= LLN AT BASELINE	56 Participants	3 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	32 Participants	2 Participants	—
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH FT3/FT4 TEST MISSING	43 Participants	2 Participants	—

SECONDARY outcome

Timeframe: From treatment assignment to disease progression, death or last dose date, up to approximately 16 months

Time to Treatment Failure is defined as the minimum of the time from treatment assignment to disease progression (determined by investigator assessments using RECIST 1.1), death or last dose date if a participant progressed, died or discontinued from treatment for any reasons other than "maximum clinical benefit" and "administrative reasons by sponsor". TTF is censored at the last dose date for participants who continued on treatment without progression (per RECIST 1.1) or death at the time of the database lock. Tumor PD-L1 protein expression was measured by immunohistochemistry (IHC).

Outcome measures

Outcome measures
Measure	Non-HBV Participants n=383 Participants Non-Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	HBV Participants n=17 Participants Hepatitis B Virus (HBV) participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.	All Treated Participants n=400 Participants All treated participants who received Nivolumab 240 mg monotherapy/30 minute IV infusion every 2 weeks. Treatment will be given up to 24 months in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab could be reinitiated as per the initial schedule for subsequent disease progression and administered for up to 1 additional year.
Time to Treatment Failure (TTF) All treated participants	2.23 Months Interval 1.94 to 3.52	1.97 Months Interval 1.41 to 10.22	2.10 Months Interval 1.94 to 3.52
Time to Treatment Failure (TTF) Squamous Tumor Histology	—	—	3.68 Months Interval 2.1 to 5.45
Time to Treatment Failure (TTF) Non-Squamous Tumor Histology	—	—	1.94 Months Interval 1.87 to 2.5
Time to Treatment Failure (TTF) EGFR Mutation Positive	—	—	1.86 Months Interval 1.68 to 3.65
Time to Treatment Failure (TTF) ALK Translocation Positive	—	—	1.91 Months Interval 1.28 to 16.36
Time to Treatment Failure (TTF) PD-L1 < 1%	—	—	1.97 Months Interval 1.87 to 2.92
Time to Treatment Failure (TTF) PD-L1 ≥ 1%	—	—	3.68 Months Interval 2.17 to 5.55
Time to Treatment Failure (TTF) PD-L1 < 5%	—	—	1.97 Months Interval 1.87 to 3.06
Time to Treatment Failure (TTF) PD-L1 ≥ 5%	—	—	3.68 Months Interval 2.23 to 5.55
Time to Treatment Failure (TTF) PD-L1 < 10%	—	—	1.97 Months Interval 1.87 to 3.09
Time to Treatment Failure (TTF) PD-L1 ≥ 10%	—	—	3.75 Months Interval 2.23 to 5.55
Time to Treatment Failure (TTF) PD-L1 < 50%	—	—	2.14 Months Interval 1.91 to 3.58
Time to Treatment Failure (TTF) PD-L1 ≥ 50%	—	—	4.11 Months Interval 2.0 to 6.01

Adverse Events

Non-HBV Participants

Serious events: 157 serious events

Other events: 359 other events

Deaths: 270 deaths

HBV Participants

Serious events: 12 serious events

Other events: 17 other events

Deaths: 9 deaths

TOTAL

Serious events: 169 serious events

Other events: 376 other events

Deaths: 279 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER