Melanoma
Conditions
Keywords
Cancer, Advanced Cancer
Brief summary
The purpose of this study is to determine whether relatlimab in combination with nivolumab is more effective than nivolumab monotherapy in treating unresectable melanoma or melanoma that has spread.
Interventions
BIOLOGICALRelatlimab
Specified dose on specified day
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Participants must have histologically confirmed Stage III (unresectable) or Stage IV melanoma, per the AJCC staging system * Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma * Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses
Exclusion criteria
* Participants must not have active brain metastases or leptomeningeal metastases * Participants must not have uveal melanoma * Participants must not have an active, known, or suspected autoimmune disease Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization to date of first documented tumor progression or death (up to approximately 33 months) | Progression Free Survival (PFS) is defined as the time between the date of randomization and the date of first documented tumor progression, assessed by a blinded independent central review (BICR) (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From randomization up to approximately 3 years | Objective response rate (ORR) is defined as the number of randomized subjects who achieve a best response of complete response (CR) or partial response (PR) based on BICR assessments (using RECIST v1.1 criteria). |
| Overall Survival (OS) | From randomization to the date of death (up to approximately 3 years) | Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. For subjects that are alive, their survival time will be censored at the date of last contact (last known alive date). |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | From first dose to 30 days after last dose of study therapy (up to approximately 33 months) | The number of participants experiencing adverse events (AEs) leading to discontinuation. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| The Number of Participant Deaths in the Study | From first dose up to approximately 33 months | The number of participant deaths in the study. |
| The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | From first dose to 30 days after last dose of study therapy (up to approximately 33 months) | The number of participants with clinical laboratory test abnormalities in specific liver tests based on US conventional units. |
| The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | From first dose to 30 days after last dose of study therapy (up to approximately 33 months) | The number of participants with clinical laboratory test abnormalities in specific thyroid tests based on US conventional units. |
| The Number of Participants Experiencing Adverse Events (AEs) | From first dose to 30 days after last dose of study therapy (up to approximately 33 months) | The number of participants experiencing adverse events (AEs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| The Number of Participants Experiencing Serious Adverse Events (SAEs) | From first dose to 30 days after last dose of study therapy (up to approximately 33 months) | The number of participants experiencing serious adverse events (SAEs). 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, is an important medical event. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Denmark, Finland, France, Germany, Greece, Israel, Italy, Mexico, New Zealand, Norway, Poland, Romania, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
714 Participants were randomized and received study treatment
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Relatlimab + Nivolumab Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W).
For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents \< 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg. | 355 |
| Arm B: Nivolumab Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W).
Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents \< 40 kg, dosing is 6 mg/kg. | 359 |
| Total | 714 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 107 | 118 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Not reported | 1 | 0 |
| Overall Study | Other reasons | 1 | 0 |
| Overall Study | Participant Withdrew Consent | 4 | 9 |
Baseline characteristics
| Characteristic | Arm B: Nivolumab | Total | Arm A: Relatlimab + Nivolumab |
|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 14 | 61.2 years STANDARD_DEVIATION 14 | 61.2 years STANDARD_DEVIATION 14.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 47 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 147 Participants | 291 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 192 Participants | 376 Participants | 184 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 18 Participants | 13 Participants |
| Race (NIH/OMB) White | 348 Participants | 690 Participants | 342 Participants |
| Sex: Female, Male Female | 153 Participants | 298 Participants | 145 Participants |
| Sex: Female, Male Male | 206 Participants | 416 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 108 / 355 | 119 / 359 |
| other Total, other adverse events | 314 / 355 | 298 / 359 |
| serious Total, serious adverse events | 155 / 355 | 140 / 359 |
Outcome results
Primary
Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as the time between the date of randomization and the date of first documented tumor progression, assessed by a blinded independent central review (BICR) (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death.
Time frame: From randomization to date of first documented tumor progression or death (up to approximately 33 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Relatlimab + Nivolumab | Progression Free Survival (PFS) | 10.12 Months |
| Arm B: Nivolumab | Progression Free Survival (PFS) | 4.63 Months |
p-value: 0.005595% CI: [0.62, 0.92]Log Rank
Secondary
Overall Response Rate (ORR)
Objective response rate (ORR) is defined as the number of randomized subjects who achieve a best response of complete response (CR) or partial response (PR) based on BICR assessments (using RECIST v1.1 criteria).
Time frame: From randomization up to approximately 3 years
Secondary
Overall Survival (OS)
Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. For subjects that are alive, their survival time will be censored at the date of last contact (last known alive date).
Time frame: From randomization to the date of death (up to approximately 3 years)
Other Pre-specified
The Number of Participant Deaths in the Study
The number of participant deaths in the study.
Time frame: From first dose up to approximately 33 months
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Relatlimab + Nivolumab | The Number of Participant Deaths in the Study | 108 Participants |
| Arm B: Nivolumab | The Number of Participant Deaths in the Study | 119 Participants |
Other Pre-specified
The Number of Participants Experiencing Adverse Events (AEs)
The number of participants experiencing adverse events (AEs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 33 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Adverse Events (AEs) | 345 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Adverse Events (AEs) | 339 Participants |
Other Pre-specified
The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
The number of participants experiencing adverse events (AEs) leading to discontinuation. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 33 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | 69 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | 41 Participants |
Other Pre-specified
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
The number of participants with clinical laboratory test abnormalities in specific liver tests based on US conventional units.
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 33 months)
Population: All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 3XULN | 26 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST> 5XULN | 11 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST> 10XULN | 4 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 20XULN | 0 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2XULN | 2 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 34 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN IN 1 DAY | 2 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN IN 30 DAYS | 2 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 2 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 2 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN IN 30 DAYS | 2 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 3XULN | 15 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 30 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST> 5XULN | 7 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 1 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST> 10XULN | 4 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN IN 1 DAY | 2 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 20XULN | 2 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 1 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2XULN | 5 Participants |
Other Pre-specified
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests
The number of participants with clinical laboratory test abnormalities in specific thyroid tests based on US conventional units.
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 33 months)
Population: All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 89 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN | 51 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 106 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH TSH <= ULN AT BASELINE | 84 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN | 63 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 7 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH FT3/FT4 TEST MISSING | 8 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH TSH >= LLN AT BASELINE | 79 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 6 Participants |
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH FT3/FT4 TEST MISSING | 11 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 3 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH TSH >= LLN AT BASELINE | 78 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 7 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN | 40 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH FT3/FT4 TEST MISSING | 7 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 106 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH FT3/FT4 TEST MISSING | 9 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH TSH <= ULN AT BASELINE | 82 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 84 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN | 48 Participants |
Other Pre-specified
The Number of Participants Experiencing Serious Adverse Events (SAEs)
The number of participants experiencing serious adverse events (SAEs). 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, is an important medical event.
Time frame: From first dose to 30 days after last dose of study therapy (up to approximately 33 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Relatlimab + Nivolumab | The Number of Participants Experiencing Serious Adverse Events (SAEs) | 121 Participants |
| Arm B: Nivolumab | The Number of Participants Experiencing Serious Adverse Events (SAEs) | 105 Participants |