Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067)

A Phase 3, Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab Versus Ipilimumab Monotherapy in Subjects With Previously Untreated Unresectable or Metastatic Melanoma

The purpose of this study is to show that Nivolumab and/or Nivolumab in combination with Ipilimumab will extend progression free survival and overall survival compared to Ipilimumab alone.

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable or Metastatic Melanoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Biological: Placebo for Nivolumab; Biological: Placebo for Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 1296
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution - 0017
    • Coffs Harbour, New South Wales, Australia, 2450
      • Local Institution - 0031
    • Gateshead, New South Wales, Australia, 2290
      • Local Institution - 0028
    • Macquarie University, New South Wales, Australia, 2109
      • Local Institution - 0023
    • North Sydney, New South Wales, Australia, 2060
      • Local Institution - 0138
  • Queensland
    • Brisbane, Queensland, Australia, 4120
      • Local Institution - 0019
    • Southport, Queensland, Australia, 4215
      • Local Institution - 0022
    • Woolloongabba, Queensland, Australia, 4102
      • Local Institution - 0018
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution - 0020
    • Kurralta Park, South Australia, Australia, 5037
      • Local Institution - 0025
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Local Institution - 0024
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0016
    • Melbourne, Victoria, Australia, 3000
      • Local Institution - 0026
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution - 0021
• Austria
  • Salzburg, Austria, 5020
    • Local Institution - 0148
  • Wien, Austria, 1090
    • Local Institution - 0145
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution - 0003
  • Bruxelles, Belgium, 1200
    • Local Institution - 0002
  • Edegem, Belgium, 2650
    • Local Institution - 0004
  • Gent, Belgium, 9000
    • Local Institution - 0005
  • Leuven, Belgium, 3000
    • Local Institution - 0103
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0140
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution - 0165
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Local Institution - 0141
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 0143
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0166
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Local Institution - 0139
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Local Institution - 0142
• Czechia
  • Brno, Czechia, 656 53
    • Local Institution - 0092
  • Hradec Kralove, Czechia, 500 05
    • Local Institution - 0091
  • Praha 2, Czechia, 128 08
    • Local Institution - 0090
  • Praha 8, Czechia, 180 81
    • Local Institution - 0167
• Denmark
  • Aarhus, Denmark, 8200
    • Local Institution - 0076
  • Herlev, Denmark, 2730
    • Local Institution - 0078
  • Odense, Denmark, 5000
    • Local Institution - 0077
• Finland
  • Tampere, Finland, 33521
    • Local Institution - 0169
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00290
      • Local Institution - 0071
• France
  • Boulogne Billancourt, France, 92104
    • Local Institution - 0125
  • Marseille Cedex 5, France, 13385
    • Local Institution - 0126
  • Nantes Cedex, France, 44093
    • Local Institution - 0056
  • Paris Cedex 10, France, 75475
    • Local Institution - 0058
  • Pierre Benite, France, 69310
    • Local Institution - 0124
  • Rennes, France, 35042
    • Local Institution - 0127
  • Villejuif, France, 94805
    • Local Institution
• Germany
  • Buxtehude, Germany, 21614
    • Local Institution - 0162
  • Erfurt, Germany, 99089
    • Local Institution - 0161
  • Erlangen, Germany, 91054
    • Local Institution - 0171
  • Essen, Germany, 45147
    • Local Institution - 0156
  • Hannover, Germany, 30625
    • Local Institution - 0159
  • Heidelberg, Germany, 69120
    • Local Institution - 0157
  • Kiel, Germany, 24105
    • Local Institution - 0158
  • Leipzig, Germany, 04103
    • Local Institution - 0178
  • Munchen, Germany, 80337
    • Local Institution - 0160
  • Tuebingen, Germany, 72076
    • Local Institution - 0134
• Ireland
  • Cork, Ireland, T12DFK4
    • Local Institution - 0033
  • Dublin, Ireland, 01
    • Local Institution - 0168
  • Dublin, Ireland, 7
    • Local Institution - 0036
  • Dublin, Ireland
    • Local Institution - 0034
  • Galway, Ireland
    • Local Institution - 0032
  • Dublin
    • Dublin 9, Dublin, Ireland
      • Local Institution - 0035
• Israel
  • Jerusalem, Israel, 91120
    • Local Institution - 0120
  • Tel Hashomer, Israel, 52621
    • Local Institution - 0121
• Italy
  • Bergamo, Italy, 24127
    • Local Institution - 0176
  • Genova, Italy, 16132
    • Local Institution - 0115
  • Meldola (FC), Italy, 47014
    • Local Institution - 0113
  • Milano, Italy, 20133
    • Local Institution - 0172
  • Milano, Italy, 20141
    • Local Institution - 0117
  • Napoli, Italy, 80131
    • Local Institution - 0114
  • Padova, Italy, 35128
    • Local Institution - 0118
  • Roma, Italy, 00144
    • Local Institution - 0177
  • Siena, Italy, 53100
    • Local Institution - 0116
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0010
  • Leiden, Netherlands, 2333 ZA
    • Local Institution - 0012
  • Nijmegen, Netherlands, 6525 GC
    • Local Institution - 0013
• New Zealand
  • Auckland, New Zealand, 1142
    • Local Institution - 0029
• Norway
  • Oslo, Norway, 0424
    • Local Institution - 0123
• Poland
  • Gdansk, Poland, 80-952
    • Local Institution - 0109
  • Krakow, Poland, 31-115
    • Local Institution - 0133
  • Lodz, Poland, 93-513
    • Local Institution - 0060
  • Warszawa, Poland, 02-781
    • Local Institution - 0059
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Local Institution - 0130
  • Saint Petersburg, Russian Federation, 197758
    • Local Institution - 0132
  • Samara, Russian Federation, 443031
    • Local Institution - 0131
  • St. Petersburg, Russian Federation, 198255
    • Local Institution - 0128
• Spain
  • Badalona-Barcelona, Spain, 08916
    • Local Institution - 0152
  • Barcelona, Spain, 08035
    • Local Institution - 0151
  • Barcelona, Spain, 08036
    • Local Institution - 0175
  • Madrid, Spain, 28007
    • Local Institution - 0150
  • Madrid, Spain, 28046
    • Local Institution - 0149
  • Malaga, Spain, 29010
    • Local Institution - 0153
  • Pamplona, Spain, 31008
    • Local Institution - 0147
• Sweden
  • Gothenberg, Sweden, 413 45
    • Local Institution - 0182
  • Stockholm, Sweden, 171 76
    • Local Institution - 0184
• Switzerland
  • Geneva, Switzerland, 1211
    • Local Institution - 0164
  • Lausanne, Switzerland, 1011
    • Local Institution - 0189
  • St. Gallen, Switzerland, 9007
    • Local Institution - 0186
  • Zuerich, Switzerland, 8091
    • Local Institution - 0163
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • Local Institution - 0037
  • Swansea, United Kingdom, SA2 8QA
    • Local Institution - 0040
  • Dumfries & Galloway
    • Glasgow, Dumfries & Galloway, United Kingdom, G12 0YN
      • Local Institution - 0039
  • Greater London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution - 0038
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4XB
      • Local Institution - 0119
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2JR
      • Local Institution - 0041
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Local Institution - 0122
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Local Institution - 0085
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093-0698
      • Local Institution - 0046
    • Los Angeles, California, United States, 90025
      • Local Institution - 0053
    • Los Angeles, California, United States, 90095
      • Local Institution - 0014
    • Palm Springs, California, United States, 92262
      • Comprehensive Cancer Center At Desert Regional Medical Ctr
    • Rancho Mirage, California, United States, 92270
      • Local Institution - 0066
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center Research Institute
    • San Francisco, California, United States, 94143
      • Local Institution - 0049
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0052
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0084
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Local Institution - 0098
    • Washington, District of Columbia, United States, 20010
      • Local Institution - 0183
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Local Institution - 0042
    • Orlando, Florida, United States, 32806
      • Local Institution - 0008
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0051
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Center for Cancer Medicine
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Local Institution - 0080
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0081
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0082
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0083
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0087
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Local Institution - 0187
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Local Institution - 0065
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 0067
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Local Institution - 0015
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Local Institution - 0188
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Local Institution - 0068
  • New York
    • Albany, New York, United States, 12206
      • Local Institution - 0079
    • New York, New York, United States, 10016
      • Local Institution - 0174
    • New York, New York, United States, 10020
      • Local Institution - 0070
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0047
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0048
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 0007
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 0045
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • Local Institution - 0061
    • Bethlehem, Pennsylvania, United States, 18015
      • Local Institution - 0112
    • Pittsburgh, Pennsylvania, United States, 15232
      • Hillman Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Local Institution - 0154
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0062
    • Nashville, Tennessee, United States, 37232
      • Local Institution - 0064
  • Texas
    • Dallas, Texas, United States, 75246
      • Local Institution - 0044
    • Dallas, Texas, United States, 75246
      • Texas Oncology
    • Houston, Texas, United States, 77030-4009
      • Local Institution - 0088
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Local Institution - 0089
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0054

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histologically confirmed stage III (unresectable) or stage IV melanoma
• Treatment naïve patients
• Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria
• Tumor tissue from an unresectable or metastatic site of disease for biomarker analyses
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases
• Ocular melanoma
• Subjects with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
• Prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Nivolumab+Placebo for Ipilimumab+Placebo for Nivolumab; Nivolumab 3 mg/kg solution intravenously every 2 weeks plus Placebo matching with Ipilimumab 0 mg/kg solution intravenously on weeks 1, 4 and Placebo matching with Nivolumab on weeks 4 for cycles 1 and 2, until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Biological: Nivolumab; Other Names: BMS-936558; MDX-1106; Biological: Placebo for Nivolumab; Biological: Placebo for Ipilimumab
Experimental: Arm B: Nivolumab+Ipilimumab+Placebo for Nivolumab; Nivolumab 1 mg/kg solution intravenously combined with Ipilimumab 3 mg/kg solution intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solution intravenously every 2 weeks plus Placebo matching with Nivolumab on weeks 3 and 5 for cycles 1 and 2, until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Biological: Nivolumab; Other Names: BMS-936558; MDX-1106; Biological: Ipilimumab; Other Names: BMS-734016; MDX-010; Yervoy; Biological: Placebo for Nivolumab
Experimental: Arm C: Ipilimumab+Placebo for Nivolumab; Ipilimumab 3 mg/kg solution intravenously every 3 weeks for a total of 4 doses plus Placebo matching with Nivolumab 0 mg/kg solution intravenously on weeks 3 and 5 for cycles 1 and 2, until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends (Placebo matching with Nivolumab is no longer required)	Biological: Ipilimumab; Other Names: BMS-734016; MDX-010; Yervoy; Biological: Placebo for Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the Investigator, or death due to any cause, whichever occurred first. Progression is defined, using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die were censored on their date of randomization. Participants who started anti-cancer therapy without prior reported progression were censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.	From randomization until disease progression or death, whichever occurred first (assessed up to February 2015, approximately 20 months)
Overall Survival (OS)	OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.	From randomization to date of death (Assessed up to September 2016, approximately 39 months)
Rate of Overall Survival	OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. The overall survival rate at time T (6, 12, or 24 months) was defined as the probability that a participant was alive at time T following randomization.	6, 12, and 24 months
Rate of Progression-Free Survival	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the Investigator, or death due to any cause, whichever occurred 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 die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die were censored on their date of randomization. Participants treated beyond progression were considered to have progressive disease at the time of the initial progression event regardless of subsequent tumor response. Participants who started anti-cancer therapy without a prior reported progression were censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.	6, 12, and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS data is presented as it was in Primary Outcome Measure #1. The statistical analysis following this outcome measure (#5) reports on a secondary objective comparing PFS between the Nivolumab and Nivolumab + Ipilimumab arms.	From randomization until disease progression or death, whichever occurred first (assessed up to February 2015, approximately 20 months)
Overall Survival (OS)	OS data is presented as it was in Primary Outcome Measure #2. The statistical analysis following this outcome measure (#6) reports on a secondary objective comparing OS between the Nivolumab and Nivolumab + Ipilimumab arms.	From randomization to date of death (Assessed up to September 2016, approximately 39 months)
Objective Response Rate (ORR) Per Investigator Assessment	The ORR was defined as the number of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each arm. The BOR was defined as the best response designation, as determined by the Investigator, recorded between the date of randomization and the date of progression, as assessed by the Investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurred first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response designations contributed to the BOR assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir.	From randomization until date of disease progression or the date of subsequent anti-cancer therapy, whichever occurs first (Assessed up to February 2015, approximately 20 months)
Progression-Free Survival Based on PD-L1 Expression Level	PD-L1 expression was defined as the percent of tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an IHC assay. Tumor biopsy specimens without measurable PD-L1 expression were classified as indeterminate if the staining was hampered for reasons attributed to the biology of the specimen and not because of improper specimen preparation or handling. Missing specimens, specimens that were not optimally collected (ie not evaluable), and all other specimens were classified as unknown. Participants must have been classified as PD-L1 >=5% or PD-L1 <5% per a verified IHC assay, or as indeterminate (ie not unknown), in order to be randomized.	From randomization until disease progression or death from any cause, whichever occurs first (Assessed up to September 2016, approximately 39 months)
Overall Survival Based on PD-L1 Expression Level	OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.	From randomization until date of death (Assessed up to September 2016, approximately 39 months)
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status	Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline. The mean score for all participants in an arm at a given week was subtracted from the mean score of the participants in that arm at baseline. Mean changes from baseline score is presented for all participants in an arm that remained on treatment and completed the EORTC-QLQ-C30 questionnaire at that time point.	Baseline and weeks 5, 7, 11, 13, 17, 19, 23, 25, then every 6 weeks until treatment discontinuation
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Social Functioning	Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.	Baseline and weeks 5, 7, 11, 13, 17, 19, 23, 25, then every 6 weeks until treatment discontinuation
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Cognitive Functioning	Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.	Baseline and weeks 5, 7, 11, 13, 17, 19, 23, 25, then every 6 weeks until treatment discontinuation
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Emotional Functioning	Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.	Baseline and weeks 5, 7, 11, 13, 17, 19, 23, 25, then every 6 weeks until treatment discontinuation
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Role Functioning	Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.	Baseline and weeks 5, 7, 11, 13, 17, 19, 23, 25, then every 6 weeks until treatment discontinuation
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Functioning	Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.	Baseline and weeks 5, 7, 11, 13, 17, 19, 23, 25, then every 6 weeks until treatment discontinuation

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Butler MO, Hill A, Marquez-Rodas I, Haanen JBAG, Guidoboni M, Maio M, Schoffski P, Carlino MS, Lebbe C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bas T, Ritchings C, Larkin J, Hodi FS. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol. 2022 Jan 10;40(2):127-137. doi: 10.1200/JCO.21.02229. Epub 2021 Nov 24.
• Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hogg D, Hill A, Marquez-Rodas I, Haanen J, Guidoboni M, Maio M, Schoffski P, Carlino MS, Lebbe C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bastholt L, Rizzo JI, Balogh A, Moshyk A, Hodi FS, Wolchok JD. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019 Oct 17;381(16):1535-1546. doi: 10.1056/NEJMoa1910836. Epub 2019 Sep 28.
• Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, Lao CD, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hill A, Hogg D, Marquez-Rodas I, Jiang J, Rizzo J, Larkin J, Wolchok JD. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1480-1492. doi: 10.1016/S1470-2045(18)30700-9. Epub 2018 Oct 22. Erratum In: Lancet Oncol. 2018 Dec;19(12):e668. Lancet Oncol. 2018 Nov;19(11):e581.
• Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbe C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-1356. doi: 10.1056/NEJMoa1709684. Epub 2017 Sep 11. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185.
• Long GV, Weber JS, Larkin J, Atkinson V, Grob JJ, Schadendorf D, Dummer R, Robert C, Marquez-Rodas I, McNeil C, Schmidt H, Briscoe K, Baurain JF, Hodi FS, Wolchok JD. Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials. JAMA Oncol. 2017 Nov 1;3(11):1511-1519. doi: 10.1001/jamaoncol.2017.1588.
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Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: April 29, 2013
• First Submitted That Met QC Criteria: April 30, 2013
• First Posted (Estimated): May 1, 2013

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-067; 2012-005371-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No