Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma (CheckMate76K)

• ClinicalTrials.gov Identifier: NCT04099251
• Recruitment Status: Active, not recruiting
• First Posted: September 23, 2019
• Results First Posted: July 27, 2023
• Last Update Posted: November 14, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: September 20, 2019
• First Posted Date: September 23, 2019
• Results First Submitted Date: June 26, 2023
• Results First Posted Date: July 27, 2023
• Last Update Posted Date: November 14, 2023
• Actual Study Start Date: October 28, 2019
• Actual Primary Completion Date: June 28, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 26, 2023)

Recurrence Free Survival (RFS) [ Time Frame: From randomization up to the date of first recurrence, new primary melanoma, or death (whatever the cause), whichever occurs first (up to 32 months) ]

Recurrence Free Survival (RFS) is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (whatever the cause), whichever occurs first. For participants who remain alive and whose disease has not recurred or did not die, RFS will be censored on the date of last evaluable disease assessment. For those participants who remained alive and had no recorded post-randomization tumor assessment, RFS will be censored on the day of randomization.

Original Primary Outcome Measures (submitted: September 20, 2019)

• Recurrence-Free Survival (RFS) [ Time Frame: approxiatemately 51 months ]
• Number of other safety biomarkers [ Time Frame: Up to 5 years ]

Current Secondary Outcome Measures (submitted: July 25, 2023)

• Distant Metastasis-Free Survival (DMFS) [ Time Frame: From randomization up to the date of first distant metastasis or date of death (whatever the cause), whichever occurs first (up to approximately 32 months) ]
  Investigator-assessed distant metastasis-free survival (DMFS) is defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants with no baseline disease assessment, no on-study disease assessments and no death, and no distant metastasis and no death will be censored. Participants with no baseline disease assessment and no on-study disease assessments and death are censored on the date of randomization. Participants with no recurrence and no death will be censored on the date of their last evaluable disease assessment.
• Duration of Treatment on Next Line Therapy Per Investigator Assessment [ Time Frame: From first dose date of next-line therapy to last dose date of next-line therapy (up to approximately 32 months) ]
  Duration of treatment is an investigator-assessed outcome of next-line therapy (NLT) defined as the time from first dose date of NLT to last dose date of NLT. Participants who did not stop the NLT were censored.
• Progression-Free Survival Through Next-Line Therapy [ Time Frame: From randomization to recurrence/objective disease progression after the start of the next-line therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first (up to approximately 32 months) ]
  Progression-free survival through next-line therapy (PFS2) is defined as the time from randomization to recurrence/objective disease progression after the start of the next-line of systemic anti-cancer therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first. Participants who did not receive subsequent systemic anti-cancer therapy who died will be considered as having the event on the date of death. Participants who received subsequent systemic anti-cancer therapy who had a disease progression after the start of therapy will be considered as having the event on the date of disease progression. Participants who died or started second next-line therapy, the date of death or start date of second next-line therapy will be the event date, whichever is earlier. Participants who did not experience disease progression, death, or second next-line therapy will be censored on the last known alive date.
• Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  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.
• Number of Participants Experiencing Adverse Events Leading to Discontinuation [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
• Number of Participants Experiencing Select Adverse Events [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  The number of participants experiencing all-cause select adverse events (AEs). An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
• Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  A Serious Adverse Events (SAE) is defined as any untoward or unfavorable medical occurrence in a participants that results in death, is life threatening, or places the participant at immediate risk of death from the event as it occurred, requires or prolongs hospitalization, causes persistent or significant disability or incapacity, results in congenital anomalies or birth defects, and is another condition which investigators judge to represent significant hazards.
• Number of Participants Experiencing Death [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  All study participants who died during the blinded phase of the study following treatment.
• Number of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities in Selected Hematology Parameters [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  The number of participants experiencing Grade 3 or 4 laboratory abnormalities in the specific pre-determined hematology tests.
• Number of Participants Experiencing Laboratory Abnormalities in Selected Liver Parameters [ Time Frame: From first dose up to 30 days post last dose of the blinded phase (up to 13 months) ]
  The number of participants experiencing laboratory abnormalities in the specific pre-determined liver tests.
• Overall Survival (OS) [ Time Frame: From randomization up to the date of death or the last date the participant was known to be alive ]
  OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.

Original Secondary Outcome Measures (submitted: September 20, 2019)

• Overall survival (OS) [ Time Frame: Up to 5 years ]
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 5 years ]
• Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 5 years ]
• Distant Metastases-Free Survival (DMFS) [ Time Frame: Up to 5 years ]
• Objective Response Rates (ORR) [ Time Frame: Up to 5 years ]
• Outcomes on Next-Line therapies (Objective response rate [if applicable], Duration of treatment on next-line therapies, Progression-Free Survival 2) [ Time Frame: Up to 5 years ]
• Incidence of change in Vital Signs [ Time Frame: Up to 5 years ]
• Incidence of change in Electrocardiograms (ECGs) [ Time Frame: Up to 5 years ]
• Incidence of change in biomarkers [ Time Frame: Up to 5 years ]
• Incidence of change in clinical laboratory values [ Time Frame: Up to 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma
• Official Title: A Phase 3, Randomized, Double-Blind Study of Adjuvant Immunotherapy With Nivolumab Versus Placebo After Complete Resection of Stage IIB/C Melanoma
• Brief Summary: The purpose of this study is to determine the effectiveness of nivolumab adjuvant immunotherapy compared to placebo in adults and pediatric participants after complete resection of Stage IIB/C melanoma with no evidence of disease (NED) who are at high risk for recurrence.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Biological: Nivolumab
  Specified dose on specified days
  Other Name: Opdivo
• Other: Placebo
  Specified dose on specified days

Study Arms

• Experimental: Nivolumab
  Intervention: Biological: Nivolumab
• Placebo Comparator: Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 12, 2021): 790
• Original Estimated Enrollment (submitted: September 20, 2019): 1000
• Estimated Study Completion Date: June 29, 2027
• Actual Primary Completion Date: June 28, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Had a negative sentinel lymph node biopsy
• Participant has not been previously treated for melanoma
• ECOG 0 or 1
• Participants must have been diagnosed with histologically confirmed, Resected, Stage IIB/C cutaneous melanoma

Exclusion Criteria:

• History of ocular or mucosal melanoma.
• Pregnant or nursing women
• Participants with active known or suspected autoimmune disease
• Known history of allergy or hypersensitivity to study drug components
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or agents that target IL-2 pathways, T-cell stimulators, or checkpoint pathways

Other protocol defined inclusion/exclusion criteria 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: Australia, Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Norway, Poland, Romania, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04099251
• Other Study ID Numbers: CA209-76K; 2019-001230-34 ( EudraCT Number ); U1111-1229-8927 ( Other Identifier: UTN 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: November 2023