Trial Outcomes & Findings for A Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC) (NCT NCT04623775)

Last Updated: 2025-10-20

Results Overview

Percentage of participants with treatment related adverse events (TRAEs) leading to discontinuation within 12 weeks of first dose. AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be determined for severity according to the NCI CTCAE v5.0.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

468 participants

Primary outcome timeframe

from first dose to 12 weeks after first dose

Results posted on

2025-10-20

Participant Flow

468 Randomized and 463 Treated

Participant milestones

Participant milestones
Measure	Part 1: Treatment A Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT	Part 2: Treatment C Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT	Part 2: Treatment D Nivo 360mg Q3W + Histology Based PDCT
Randomization STARTED	79	80	158	151
Randomization COMPLETED	77	79	158	149
Randomization NOT COMPLETED	2	1	0	2
Treatment Period STARTED	77	79	158	149
Treatment Period COMPLETED	9	12	61	60
Treatment Period NOT COMPLETED	68	67	97	89

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Treatment A Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT	Part 2: Treatment C Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT	Part 2: Treatment D Nivo 360mg Q3W + Histology Based PDCT
Randomization No Longer Meets Study Criteria	2	1	0	0
Randomization Withdrew Consent	0	0	0	1
Randomization Other Reasons	0	0	0	1
Treatment Period participant withdrew consent	4	0	1	2
Treatment Period Death	3	1	4	2
Treatment Period Lost to Follow-up	0	2	0	0
Treatment Period poor/non compliance	0	0	1	0
Treatment Period participant no longer meets study criteria	0	1	0	0
Treatment Period administrative reasons by sponsor	3	2	0	0
Treatment Period other reasons	2	0	1	1
Treatment Period disease progression	40	35	63	63
Treatment Period study drug toxicity	12	15	13	12
Treatment Period AE unrelated to study drug	4	9	12	9
Treatment Period participant request to discontinue treatment	0	2	2	0

Baseline Characteristics

A Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Treatment A n=79 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=80 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT	Part 2: Treatment C n=158 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT	Part 2: Treatment D n=151 Participants Nivo 360mg Q3W + Histology Based PDCT	Total n=468 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=5 Participants	42 Participants n=7 Participants	73 Participants n=5 Participants	72 Participants n=4 Participants	224 Participants n=21 Participants
Age, Categorical >=65 years	42 Participants n=5 Participants	38 Participants n=7 Participants	85 Participants n=5 Participants	79 Participants n=4 Participants	244 Participants n=21 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	32 Participants n=7 Participants	55 Participants n=5 Participants	57 Participants n=4 Participants	172 Participants n=21 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	48 Participants n=7 Participants	103 Participants n=5 Participants	94 Participants n=4 Participants	296 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants	12 Participants n=7 Participants	31 Participants n=5 Participants	28 Participants n=4 Participants	87 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	44 Participants n=7 Participants	91 Participants n=5 Participants	88 Participants n=4 Participants	260 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants	24 Participants n=7 Participants	36 Participants n=5 Participants	35 Participants n=4 Participants	121 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	75 Participants n=5 Participants	77 Participants n=7 Participants	148 Participants n=5 Participants	141 Participants n=4 Participants	441 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	21 Participants n=21 Participants

PRIMARY outcome

Timeframe: from first dose to 12 weeks after first dose

Population: All Treated Dose-Safety Evaluable participants in part 1

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=71 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=66 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
TRAEs Leading to Discontinuation Within 12 Weeks of First Dose in Part 1	5.6 Percentage of Participants Interval 1.6 to 13.8	12.1 Percentage of Participants Interval 5.4 to 22.5

PRIMARY outcome

Timeframe: Approximately 14.8 Months

Population: All randomized participants in Part 2

Objective Response Rate (ORR) per RECIST v1.1 by BICR is defined as the number of participants in the randomized population who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1) divided by the number of participants in the population. BOR is defined as the best response, as determined by the BICR, recorded between the date of randomization and the date of first objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=151 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
ORR Per RECISTS v1.1 by BICR in Part 2	50.6 Percentage of Participants Interval 43.8 to 57.4	43.0 Percentage of Participants Interval 36.2 to 50.1

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)

Population: All treated participants in Part 1

Number of participants with treatment related adverse events (TRAEs) leading to discontinuation based on grade. AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be determined for severity according to the NCI CTCAE v5.0

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=77 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=79 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
TRAEs Leading to Discontinuation in Part 1 Any Grade	21 Participants	18 Participants
TRAEs Leading to Discontinuation in Part 1 Grade 3 to 4	13 Participants	12 Participants
TRAEs Leading to Discontinuation in Part 1 Grade 5	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)

Population: All treated participants in Part 1

Number of participants with a treatment related AE in part 1. AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be determined for severity according to the NCI CTCAE v5.0

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=77 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=79 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With a Treatment Related AEs in Part 1	75 Participants	76 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)

Population: All treated participants in Part 1

A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[e.g., medical, surgical\] to prevent one of the other serious outcomes listed in the definition). Grading will be determined for severity according to the NCI CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=77 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=79 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With Treatment Releted SAEs in Part 1 Any Grade	20 Participants	24 Participants
Number of Participants With Treatment Releted SAEs in Part 1 Grade 3 to 4	14 Participants	18 Participants
Number of Participants With Treatment Releted SAEs in Part 1 Grade 5	2 Participants	4 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)

Population: All treated participants in Part 1

AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Select Adverse Events (AEs) will be determined for severity according to the NCI CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=77 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=79 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With Treatment Releted Select AEs in Part 1 Gastrointestinal	18 Participants	15 Participants
Number of Participants With Treatment Releted Select AEs in Part 1 Hepatic	26 Participants	18 Participants
Number of Participants With Treatment Releted Select AEs in Part 1 Pulmonary	4 Participants	5 Participants
Number of Participants With Treatment Releted Select AEs in Part 1 Renal	9 Participants	4 Participants
Number of Participants With Treatment Releted Select AEs in Part 1 Skin	24 Participants	18 Participants
Number of Participants With Treatment Releted Select AEs in Part 1 Hypersensitivity/Infusion Reaction	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Approximately 14.8 Months

Population: All randomized participants in Part 2

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=151 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 PD-L1 <1%	48.6 Percentage of Participants Interval 38.2 to 59.0	44.8 Percentage of Participants Interval 34.4 to 55.5
ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 PD-L1 >= 1%	53.2 Percentage of Participants Interval 43.3 to 62.8	39.4 Percentage of Participants Interval 29.7 to 49.9
ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 Not Quantifiable	44.4 Percentage of Participants Interval 16.9 to 74.9	53.8 Percentage of Participants Interval 28.7 to 77.6

SECONDARY outcome

Timeframe: Approximately up to 13.7 months

Population: All randomized participants in Part 2

Duration of Response (DOR) will be assessed by BICR. It is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the first objectively documented tumor progression as determined by the BICR (per RECIST v1.1), or death due to any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=151 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
DoR Per RECISTS v1.1 by BICR in Part 2	8.41 Months Interval 7.43 to Upper limit was not reached due to an insufficient number of participants with events	7.10 Months Interval 5.62 to Upper limit was not reached due to an insufficient number of participants with events

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)

Population: All treated participants in Part 2

Number of participants with an adverse event (AE). AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be determined for severity according to the NCI CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=149 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With a AE in Part 2 Grade 3 to 4	90 Participants	85 Participants
Number of Participants With a AE in Part 2 Any Grade	158 Participants	147 Participants
Number of Participants With a AE in Part 2 Grade 5	26 Participants	19 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)

Population: All treated participants in Part 2

AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be determined for severity according to the NCI CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=149 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With a Treatment Related AEs in Part 2 Any Grade	147 Participants	138 Participants
Number of Participants With a Treatment Related AEs in Part 2 Grade 3 to 4	79 Participants	78 Participants
Number of Participants With a Treatment Related AEs in Part 2 Grade 5	4 Participants	4 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)

Population: All treated participants in Part 2

SAE is defined as a life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe). SAEs can also result in death. The AE requires inpatient hospitalization or causes prolongation of existing hospitalization. Results in persistent or significant disability/incapacity. Is a congenital anomaly/birth defect. Is an important medical event (defined as a medical event(s) that may not be immediately lifethreatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[e.g., medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.) Grading will be determined for severity according to the NCI CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=149 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With a Treatment Related SAEs in Part 2 Any Grade	34 Participants	36 Participants
Number of Participants With a Treatment Related SAEs in Part 2 Grade 3 to 4	26 Participants	28 Participants
Number of Participants With a Treatment Related SAEs in Part 2 Grade 5	4 Participants	4 Participants

SECONDARY outcome

Timeframe: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)

Population: All treated participants in Part 2

IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity. Grading will be determined for severity according to the NCI CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Part 1: Treatment A n=158 Participants Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT	Part 1: Treatment B n=149 Participants Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Adrenal Insufficiency	2 Participants	3 Participants
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Hypothyroidism/Thyroiditis	22 Participants	13 Participants
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Hypothyroidism	21 Participants	13 Participants
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Thyroiditis	2 Participants	0 Participants
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Diabetes Mellitus	1 Participants	0 Participants
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Hyperthyroidism	14 Participants	3 Participants
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 Hypophysitis	0 Participants	1 Participants

SECONDARY outcome

Timeframe: On Going

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Ongoing

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Ongoing

Progression Free Survival is defined as the time between the date of randomization and the first date of documented progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Ongoing

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Ongoing

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Ongoing

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Ongoing

Outcome measures

Outcome data not reported

Adverse Events

Part 1: Treatment A

Serious events: 46 serious events

Other events: 74 other events

Deaths: 47 deaths

Part 1: Treatment B

Serious events: 52 serious events

Other events: 78 other events

Deaths: 46 deaths

Part 2: Treatment C

Serious events: 103 serious events

Other events: 151 other events

Deaths: 79 deaths

Part 2: Treatment D

Serious events: 81 serious events

Other events: 145 other events

Deaths: 70 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: 1-855-907-3286

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