A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047)

• ClinicalTrials.gov Identifier: NCT03470922
• Recruitment Status: Active, not recruiting
• First Posted: March 20, 2018
• Results First Posted: March 29, 2022
• Last Update Posted: September 21, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: March 14, 2018
• First Posted Date: March 20, 2018
• Results First Submitted Date: January 25, 2022
• Results First Posted Date: March 29, 2022
• Last Update Posted Date: September 21, 2023
• Actual Study Start Date: April 11, 2018
• Actual Primary Completion Date: January 25, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2022)

Progression Free Survival (PFS) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: March 14, 2018)

• Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
  Phase 3 portion of trial. Assessed by a Blinded Independent Central Review (BICR)
• Overall Response Rate (ORR) [ Time Frame: Up to 5 years ]
  Phase 2 portion of trial, assessed by a BICR

Current Secondary Outcome Measures (submitted: January 25, 2022)

• Overall Survival (OS) [ Time Frame: 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").
• Overall Response Rate (ORR) [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: March 14, 2018)

• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  Phase 3 portion of trial. To compare BMS-986213 to nivolumab monotherapy
• ORR [ Time Frame: Up to 5 years ]
  Phase 3 portion of trial, assessed by a BICR
• ORR [ Time Frame: Up to 5 years ]
  Phase 2 portion of trial, assessed by a BICR in subgroups
• Duration of Response (DOR) [ Time Frame: Up to 5 years ]
  Phase 2 portion of trial. In the randomized population and in subgroups
• Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
  Phase 2 portion of trial. In the randomized population and in subgroups
• PFS [ Time Frame: Up to 5 years ]
  Phase 2 portion of trial. In the randomized population and in subgroups
• OS [ Time Frame: Up to 5 years ]
  Phase 2 portion of trial. In the randomized population and in subgroups
• Nubmer of Adverse Events (AEs) [ Time Frame: Up to 5 years ]
  Phase 2 portion of the trial
• Number of Serious Adverse Events (SAEs) [ Time Frame: Up to 5 years ]
  Phase 2 portion of the trial
• Number of AEs Leading to Discontinuation [ Time Frame: Up to 5 years ]
  Phase 2 portion of the trial
• Number of Deaths [ Time Frame: Up to 5 years ]
  Phase 2 portion of the trial
• Number of Laboratory Abnormalities [ Time Frame: Up to 5 years ]
  Phase 2 portion of the trial

Current Other Pre-specified Outcome Measures (submitted: March 2, 2022)

• The Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: 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) [ Time Frame: 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.
• The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma
• Official Title: A Randomized, Double-Blind Phase 2/3 Study of Relatlimab Combined With Nivolumab Versus Nivolumab in Participants With Previously Untreated Metastatic or Unresectable Melanoma
• Brief Summary: The purpose of this study is to determine whether relatlimab in combination with nivolumab is more effective than nivolumab by itself in treating unresectable melanoma or melanoma that has spread.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Biological: Relatlimab
  Specified dose on specified day
• Biological: Nivolumab
  Specified dose on specified days

Study Arms

• Experimental: Arm A: Relatlimab + Nivolumab
  Combination
  Interventions:

  • Biological: Relatlimab
  • Biological: Nivolumab
• Experimental: Arm B: Nivolumab
  Monotherapy
  Intervention: Biological: Nivolumab

• Publications *: Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutierrez E, Rutkowski P, Gogas HJ, Lao CD, De Menezes JJ, Dalle S, Arance A, Grob JJ, Srivastava S, Abaskharoun M, Hamilton M, Keidel S, Simonsen KL, Sobiesk AM, Li B, Hodi FS, Long GV; RELATIVITY-047 Investigators. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022 Jan 6;386(1):24-34. doi: 10.1056/NEJMoa2109970.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 8, 2021): 714
• Original Estimated Enrollment (submitted: March 14, 2018): 700
• Estimated Study Completion Date: December 16, 2025
• Actual Primary Completion Date: January 25, 2021 (Final data collection date for primary outcome measure)

Eligibility 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/exclusion criteria could apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Denmark, Finland, France, Germany, Greece, Israel, Italy, Mexico, New Zealand, Norway, Poland, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03470922
• Other Study ID Numbers: CA224-047; 2017-003583-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: September 2023