Clinical trial NCT01844505: Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Unresectable or Metastatic Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-05-01
Enrollment: 945
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization until disease progression or death, whichever occurred first (assessed up to February 2015, approximately 20 months)
measure: Overall Survival (OS)
timeFrame: From randomization to date of death (Assessed up to September 2016, approximately 39 months)
measure: Rate of Overall Survival
timeFrame: 24 months
measure: Rate of Progression-Free Survival
timeFrame: 24 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization until disease progression or death, whichever occurred first (assessed up to approximately 128 months)
measure: Overall Survival (OS)
timeFrame: From randomization until death (assessed up to approximately 128 months)
measure: Objective Response Rate (ORR) Per Investigator Assessment
timeFrame: From randomization until disease progression or death, whichever occurred first (assessed up to approximately 128 months)
measure: Progression-Free Survival Based on PD-L1 Expression Level
timeFrame: From randomization until disease progression or death from any cause, whichever occurs first (Assessed up to September 2016, approximately 39 months)
measure: Overall Survival Based on PD-L1 Expression Level
timeFrame: From randomization until death (assessed up to approximately 128 months)
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status
timeFrame: Baseline (Day 1) and Week 5, 7, 11, 13, 17, 19, 23, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, 145, 151 and 157
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Social Functioning
timeFrame: Baseline (Day 1) and Week 5, 7, 11, 13, 17, 19, 23, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, 145, 151 and 157
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Cognitive Functioning
timeFrame: Baseline (Day 1) and Week 5, 7, 11, 13, 17, 19, 23, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, 145, 151 and 157
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Emotional Functioning
timeFrame: Baseline (Day 1) and Week 5, 7, 11, 13, 17, 19, 23, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, 145, 151 and 157
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Role Functioning
timeFrame: Baseline (Day 1) and Week 5, 7, 11, 13, 17, 19, 23, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, 145, 151 and 157
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Functioning
timeFrame: Baseline (Day 1) and Week 5, 7, 11, 13, 17, 19, 23, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, 145, 151 and 157
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Local Institution - 0085
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: Local Institution - 0046
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0053
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0014
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center At Desert Regional Medical Ctr
state: California
city: Rancho Mirage
country: United States
facility: Local Institution - 0066
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: San Francisco
country: United States
facility: Local Institution - 0049
state: California
city: Aurora
country: United States
facility: Local Institution - 0052
state: Colorado
city: New Haven
country: United States
facility: Local Institution - 0084
state: Connecticut
city: Washington
country: United States
facility: Local Institution - 0098
state: District of Columbia
city: Washington
country: United States
facility: Local Institution - 0183
state: District of Columbia
city: Jacksonville
country: United States
facility: Local Institution - 0042
state: Florida
city: Orlando
country: United States
facility: Local Institution - 0008
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0051
state: Georgia
city: Scarborough
country: United States
facility: Maine Center For Cancer Medicine
state: Maine
city: Lutherville
country: United States
facility: Local Institution - 0080
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0081
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0082
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0083
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0087
state: Michigan
city: Minneapolis
country: United States
facility: Local Institution - 0187
state: Minnesota
city: Jackson
country: United States
facility: Local Institution - 0065
state: Mississippi
city: Saint Louis
country: United States
facility: Local Institution - 0067
state: Missouri
city: Las Vegas
country: United States
facility: Local Institution - 0015
state: Nevada
city: Morristown
country: United States
facility: Local Institution - 0188
state: New Jersey
city: Albuquerque
country: United States
facility: Local Institution - 0068
state: New Mexico
city: Albany
country: United States
facility: Local Institution - 0079
state: New York
city: New York
country: United States
facility: Local Institution - 0174
state: New York
city: New York
country: United States
facility: Local Institution - 0070
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0047
state: North Carolina
city: Durham
country: United States
facility: Local Institution - 0048
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 0007
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0045
state: Oregon
city: Allentown
country: United States
facility: Local Institution - 0061
state: Pennsylvania
city: Bethlehem
country: United States
facility: Local Institution - 0112
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0069
state: Pennsylvania
city: Greenville
country: United States
facility: Local Institution - 0154
state: South Carolina
city: Nashville
country: United States
facility: Local Institution - 0062
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0064
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0044
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: Local Institution - 0088
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 0089
state: Utah
city: Seattle
country: United States
facility: Local Institution - 0054
state: Washington
city: Camperdown
country: Australia
facility: Local Institution - 0017
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Local Institution - 0031
state: New South Wales
city: Gateshead
country: Australia
facility: Local Institution - 0028
state: New South Wales
city: Macquarie University
country: Australia
facility: Local Institution - 0023
state: New South Wales
city: North Sydney
country: Australia
facility: Local Institution - 0138
state: New South Wales
city: Brisbane
country: Australia
facility: Local Institution - 0019
state: Queensland
city: Southport
country: Australia
facility: Local Institution - 0022
state: Queensland
city: Woolloongabba
country: Australia
facility: Local Institution - 0018
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution - 0020
state: South Australia
city: Kurralta Park
country: Australia
facility: Local Institution - 0025
state: South Australia
city: Box Hill
country: Australia
facility: Local Institution - 0024
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0016
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0026
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0021
state: Western Australia
city: Salzburg
country: Austria
facility: Local Institution - 0148
city: Wien
country: Austria
facility: Local Institution - 0145
city: Brussels
country: Belgium
facility: Local Institution - 0003
city: Bruxelles
country: Belgium
facility: Local Institution - 0002
city: Edegem
country: Belgium
facility: Local Institution - 0004
city: Gent
country: Belgium
facility: Local Institution - 0005
city: Leuven
country: Belgium
facility: Local Institution - 0103
city: Edmonton
country: Canada
facility: Local Institution - 0140
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution - 0165
state: British Columbia
city: London
country: Canada
facility: Local Institution - 0141
state: Ontario
city: Ottawa
country: Canada
facility: Local Institution - 0143
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0166
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0139
state: Quebec
city: Quebec City
country: Canada
facility: Local Institution - 0142
state: Quebec
city: Brno
country: Czechia
facility: Local Institution - 0092
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0091
city: Praha 2
country: Czechia
facility: Local Institution - 0090
city: Praha 8
country: Czechia
facility: Local Institution - 0167
city: Aarhus
country: Denmark
facility: Local Institution - 0076
city: Herlev
country: Denmark
facility: Local Institution - 0078
city: Odense
country: Denmark
facility: Local Institution - 0077
city: Helsinki
country: Finland
facility: Local Institution - 0071
state: Uusimaa
city: Tampere
country: Finland
facility: Local Institution - 0169
city: Boulogne Billancourt
country: France
facility: Local Institution - 0125
city: Marseille Cedex 5
country: France
facility: Local Institution - 0126
city: Nantes Cedex
country: France
facility: Local Institution - 0056
city: Paris Cedex 10
country: France
facility: Local Institution - 0058
city: Pierre Benite
country: France
facility: Local Institution - 0124
city: Rennes
country: France
facility: Local Institution - 0127
city: Villejuif
country: France
facility: Local Institution
city: Buxtehude
country: Germany
facility: Local Institution - 0162
city: Erfurt
country: Germany
facility: Local Institution - 0161
city: Erlangen
country: Germany
facility: Local Institution - 0171
city: Essen
country: Germany
facility: Local Institution - 0156
city: Hannover
country: Germany
facility: Local Institution - 0159
city: Heidelberg
country: Germany
facility: Local Institution - 0157
city: Kiel
country: Germany
facility: Local Institution - 0158
city: Leipzig
country: Germany
facility: Local Institution - 0178
city: Munchen
country: Germany
facility: Local Institution - 0160
city: Tuebingen
country: Germany
facility: Local Institution - 0134
city: Dublin 9
country: Ireland
facility: Local Institution - 0035
state: Dublin
city: Cork
country: Ireland
facility: Local Institution - 0033
city: Dublin
country: Ireland
facility: Local Institution - 0168
city: Dublin
country: Ireland
facility: Local Institution - 0036
city: Dublin
country: Ireland
facility: Local Institution - 0034
city: Galway
country: Ireland
facility: Local Institution - 0032
city: Jerusalem
country: Israel
facility: Local Institution - 0120
city: Tel Hashomer
country: Israel
facility: Local Institution - 0121
city: Bergamo
country: Italy
facility: Local Institution - 0176
city: Genova
country: Italy
facility: Local Institution - 0115
city: Meldola (FC)
country: Italy
facility: Local Institution - 0113
city: Milano
country: Italy
facility: Local Institution - 0172
city: Milano
country: Italy
facility: Local Institution - 0117
city: Napoli
country: Italy
facility: Local Institution - 0114
city: Padova
country: Italy
facility: Local Institution - 0118
city: Roma
country: Italy
facility: Local Institution - 0177
city: Siena
country: Italy
facility: Local Institution - 0116
city: Amsterdam
country: Netherlands
facility: Local Institution - 0010
city: Leiden
country: Netherlands
facility: Local Institution - 0012
city: Nijmegen
country: Netherlands
facility: Local Institution - 0013
city: Auckland
country: New Zealand
facility: Local Institution - 0029
city: Oslo
country: Norway
facility: Local Institution - 0123
city: Gdansk
country: Poland
facility: Local Institution - 0109
city: Krakow
country: Poland
facility: Local Institution - 0133
city: Lodz
country: Poland
facility: Local Institution - 0060
city: Warszawa
country: Poland
facility: Local Institution - 0059
city: Moscow
country: Russian Federation
facility: Local Institution - 0130
city: Saint Petersburg
country: Russian Federation
facility: Local Institution - 0132
city: Samara
country: Russian Federation
facility: Local Institution - 0131
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 0128
city: Badalona-Barcelona
country: Spain
facility: Local Institution - 0152
city: Barcelona
country: Spain
facility: Local Institution - 0151
city: Barcelona
country: Spain
facility: Local Institution - 0175
city: Madrid
country: Spain
facility: Local Institution - 0150
city: Madrid
country: Spain
facility: Local Institution - 0149
city: Malaga
country: Spain
facility: Local Institution - 0153
city: Pamplona
country: Spain
facility: Local Institution - 0147
city: Gothenberg
country: Sweden
facility: Local Institution - 0182
city: Stockholm
country: Sweden
facility: Local Institution - 0184
city: Geneva
country: Switzerland
facility: Local Institution - 0164
city: Lausanne
country: Switzerland
facility: Local Institution - 0189
city: St. Gallen
country: Switzerland
facility: Local Institution - 0186
city: Zuerich
country: Switzerland
facility: Local Institution - 0163
city: Glasgow
country: United Kingdom
facility: Local Institution - 0039
state: Dumfries & Galloway
city: London
country: United Kingdom
facility: Local Institution - 0038
state: Greater London
city: Manchester
country: United Kingdom
facility: Local Institution - 0119
state: Greater Manchester
city: Northwood
country: United Kingdom
facility: Local Institution - 0041
state: Middlesex
city: Nottingham
country: United Kingdom
facility: Local Institution - 0122
state: Nottinghamshire
city: Cambridge
country: United Kingdom
facility: Local Institution - 0037
city: Swansea
country: United Kingdom
facility: Local Institution - 0040
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Schadendorf D, Larkin J, Wolchok J, Hodi FS, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao C, Wagstaff J, Callahan MK, Postow MA, Smylie M, Ferrucci PF, Dummer R, Hill A, Taylor F, Sabater J, Walker D, Kotapati S, Abernethy A, Long GV. Health-related quality of life results from the phase III CheckMate 067 study. Eur J Cancer. 2017 Sep;82:80-91. doi: 10.1016/j.ejca.2017.05.031. Epub 2017 Jun 23.
citation: Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185. doi: 10.1056/NEJMx180040.