Back to resultsStudy of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma (CheckMate 069)
Primary Purpose
Unresectable Melanoma, Metastatic Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nivolumab
Ipilimumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable Melanoma
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Key Inclusion Criteria:
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Histologically confirmed unresectable Stage III or Stage IV melanoma
- No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
- Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
- Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.
Key Exclusion Criteria:
- Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
- Ocular melanoma
- Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Sites / Locations
- San Francisco Oncology Associates
- Orlando Health Inc
- University Of Louisville Medical Center, Inc., Dba
- Beth Israel Deaconess Medical Center
- Dana Farber Cancer Institute
- Massachusetts General Hospital
- Washington University School Of Medicine
- Comprehensive Cancer Centers Of Nevada
- Dartmouth-Hitchcock Medical Center
- University Of New Mexico Cancer Center
- NYU Clinical Cancer Center
- Memorial Sloan Kettering Nassau
- Duke University Medical Center
- The Christ Hospital
- Oregon Health & Science University
- St. Luke's Hospital
- GHS Cancer Institute
- Huntsman Cancer Institute
- University Of Wisconsin Paul P Carbone Comprehensive Ca Ctr
- Hopital Larrey
- Institut Gustave Roussy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Nivolumab + Ipilimumab
Placebo + Ipilimumab
Arm Description
Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants
Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.
CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm).
PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Secondary Outcome Measures
Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants
PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or died were censored on the date of their last evaluable tumor assessment.
PFS values are based on Kaplan-Meier Estimates.
Objective Response Rate (ORR) - BRAF Mutant Participants
Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.
CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm).
PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Progression-Free Survival (PFS) - BRAF Mutant Participants
PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or died were censored on the date of their last evaluable tumor assessment.
PFS values are based on Kaplan-Meier Estimates.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QOL) C30 Score
The EORTC QLQ-C30 version 3 is a questionnaire developed to assess the QOL of cancer patients. The questionnaire is a 30-item tool, and it comprises 6 functional subscales (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as 9 symptom subscales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).
Scores for each subscale range from 0 to 100. For the 6 functional subscales, a higher score represents a better level of functioning/health status. For the 9 symptom subscales, a lower score represents a better outcome (low level of symptomatology).
Scores for the 15 subscales are presented individually.
Full Information
NCT ID
NCT01927419
First Posted
August 20, 2013
Last Updated
February 16, 2022
Sponsor
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT01927419
Brief Title
Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma
Acronym
CheckMate 069
Official Title
Phase 2, Randomized, Double Blinded, Study of Nivolumab (BMS-936558) in Combination With Ipilimumab vs Ipilimumab Alone in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
August 23, 2013 (Actual)
Primary Completion Date
July 24, 2014 (Actual)
Study Completion Date
February 26, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary purpose of this study is to compare the objective response rate, as determined by investigators, of Nivolumab combined with Ipilimumab versus Ipilimumab monotherapy in patients with untreated, unresectable, or metastatic melanoma
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable Melanoma, Metastatic Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
142 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nivolumab + Ipilimumab
Arm Type
Experimental
Arm Description
Participants received (Part 1) 1 mg/kg of nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) 3 mg/kg of nivolumab intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Arm Title
Placebo + Ipilimumab
Arm Type
Experimental
Arm Description
Participants received (Part 1) placebo-matching nivolumab + 3 mg/kg of ipilimumab solution intravenously every 3 weeks for 4 doses (4 cycles), then (Part 2) placebo-matching nivolumab solution intravenously every 2 weeks until documented disease progression, toxicity, withdrawal of consent, or study completion.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo, BMS-936558
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Yervoy
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching nivolumab
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) - BRAF Wild-type (WT) Participants
Description
Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.
CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm).
PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame
From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS) - BRAF Wild-type (WT) Participants
Description
PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or died were censored on the date of their last evaluable tumor assessment.
PFS values are based on Kaplan-Meier Estimates.
Time Frame
From randomization to progression or death (up to approximately 88 months)
Title
Objective Response Rate (ORR) - BRAF Mutant Participants
Description
Objective Response Rate is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), assessed by the investigator by using RECIST 1.1 criteria.
CR=all target and nontarget lesions have disappeared. Lymph nodes selected must have returned to normal size (<10 mm).
PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame
From 12 weeks after Randomization, assessed every 6 weeks up to Week 49 of study treatment and then every 12 weeks until disease progression (up to approximately 76 months)
Title
Progression-Free Survival (PFS) - BRAF Mutant Participants
Description
PFS is defined as the time between the date of randomization and the first date of documented progression, as assessed by the investigator, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or died were censored on the date of their last evaluable tumor assessment.
PFS values are based on Kaplan-Meier Estimates.
Time Frame
From randomization to progression or death (up to approximately 88 months)
Title
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QOL) C30 Score
Description
The EORTC QLQ-C30 version 3 is a questionnaire developed to assess the QOL of cancer patients. The questionnaire is a 30-item tool, and it comprises 6 functional subscales (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as 9 symptom subscales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).
Scores for each subscale range from 0 to 100. For the 6 functional subscales, a higher score represents a better level of functioning/health status. For the 9 symptom subscales, a lower score represents a better outcome (low level of symptomatology).
Scores for the 15 subscales are presented individually.
Time Frame
From Baseline (prior to start of study treatment) to Week 25 after first dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Key Inclusion Criteria:
Eastern Cooperative Oncology Group performance status of 0 or 1
Histologically confirmed unresectable Stage III or Stage IV melanoma
No prior systemic anticancer therapy for unresectable or metastatic melanoma. Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized
Tumor tissue obtained in the metastatic setting or from an unresectable site must be provided for biomarker analyses and sent to the central laboratory. Biopsy should be excisional, incisional punch, or core needle. Fine needle aspirates or other cytology samples are insufficient
Known BRAF V600 mutation status as determined by an FDA-approved test. Patients with either V600 wild-type or V600 mutation-positive melanoma are eligible.
Key Exclusion Criteria:
Active brain metastases or leptomeningeal metastases. Patients with treated brain metastases are eligible if there is no evidence of progression on magnetic resonance imaging scan for at least 8 weeks after completion of treatment and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
Ocular melanoma
Patients with active, known, or suspected autoimmune disease. Those with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
San Francisco Oncology Associates
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Orlando Health Inc
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
University Of Louisville Medical Center, Inc., Dba
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University School Of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Comprehensive Cancer Centers Of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
University Of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
NYU Clinical Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
St. Luke's Hospital
City
Easton
State/Province
Pennsylvania
ZIP/Postal Code
18045
Country
United States
Facility Name
GHS Cancer Institute
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University Of Wisconsin Paul P Carbone Comprehensive Ca Ctr
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Hopital Larrey
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
34855329
Citation
Mantia CM, Werner L, Stwalley B, Ritchings C, Tarhini AA, Atkins MB, McDermott DF, Regan MM. Sensitivity of treatment-free survival to subgroup analyses in patients with advanced melanoma treated with immune checkpoint inhibitors. Melanoma Res. 2022 Feb 1;32(1):35-44. doi: 10.1097/CMR.0000000000000793.
Results Reference
derived
PubMed Identifier
27622997
Citation
Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1558-1568. doi: 10.1016/S1470-2045(16)30366-7. Epub 2016 Sep 9.
Results Reference
derived
PubMed Identifier
25891304
Citation
Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015 May 21;372(21):2006-17. doi: 10.1056/NEJMoa1414428. Epub 2015 Apr 20. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
Investigator Inquiry Form
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
Learn more about this trial
Study of Nivolumab (BMS-936558) Plus Ipilimumab Compared With Ipilimumab Alone in the Treatment of Previously Untreated, Unresectable, or Metastatic Melanoma
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