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

NCT ID: NCT01844505

Last Updated: 2025-05-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

945 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-11

Study Completion Date

2024-04-19

Brief Summary

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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.

Detailed Description

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Conditions

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Unresectable or Metastatic Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Placebo for Nivolumab

Intervention Type BIOLOGICAL

Placebo for Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

Placebo for Nivolumab

Intervention Type BIOLOGICAL

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)

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Placebo for Nivolumab

Intervention Type BIOLOGICAL

Interventions

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Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

Placebo for Nivolumab

Intervention Type BIOLOGICAL

Placebo for Ipilimumab

Intervention Type BIOLOGICAL

Other Intervention Names

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BMS-936558 MDX-1106 Yervoy BMS-734016 MDX-010

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0085

Gilbert, Arizona, United States

Site Status

University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

Local Institution - 0046

La Jolla, California, United States

Site Status

Local Institution - 0053

Los Angeles, California, United States

Site Status

Local Institution - 0014

Los Angeles, California, United States

Site Status

Comprehensive Cancer Center At Desert Regional Medical Ctr

Palm Springs, California, United States

Site Status

Local Institution - 0066

Rancho Mirage, California, United States

Site Status

California Pacific Medical Center Research Institute

San Francisco, California, United States

Site Status

Local Institution - 0049

San Francisco, California, United States

Site Status

Local Institution - 0052

Aurora, Colorado, United States

Site Status

Local Institution - 0084

New Haven, Connecticut, United States

Site Status

Local Institution - 0098

Washington D.C., District of Columbia, United States

Site Status

Local Institution - 0183

Washington D.C., District of Columbia, United States

Site Status

Local Institution - 0042

Jacksonville, Florida, United States

Site Status

Local Institution - 0008

Orlando, Florida, United States

Site Status

Local Institution - 0051

Atlanta, Georgia, United States

Site Status

Maine Center For Cancer Medicine

Scarborough, Maine, United States

Site Status

Local Institution - 0080

Lutherville, Maryland, United States

Site Status

Local Institution - 0081

Boston, Massachusetts, United States

Site Status

Local Institution - 0082

Boston, Massachusetts, United States

Site Status

Local Institution - 0083

Boston, Massachusetts, United States

Site Status

Local Institution - 0087

Ann Arbor, Michigan, United States

Site Status

Local Institution - 0187

Minneapolis, Minnesota, United States

Site Status

Local Institution - 0065

Jackson, Mississippi, United States

Site Status

Local Institution - 0067

St Louis, Missouri, United States

Site Status

Local Institution - 0015

Las Vegas, Nevada, United States

Site Status

Local Institution - 0188

Morristown, New Jersey, United States

Site Status

Local Institution - 0068

Albuquerque, New Mexico, United States

Site Status

Local Institution - 0079

Albany, New York, United States

Site Status

Local Institution - 0174

New York, New York, United States

Site Status

Local Institution - 0070

New York, New York, United States

Site Status

Local Institution - 0047

Charlotte, North Carolina, United States

Site Status

Local Institution - 0048

Durham, North Carolina, United States

Site Status

Local Institution - 0007

Cleveland, Ohio, United States

Site Status

Local Institution - 0045

Portland, Oregon, United States

Site Status

Local Institution - 0061

Allentown, Pennsylvania, United States

Site Status

Local Institution - 0112

Bethlehem, Pennsylvania, United States

Site Status

Local Institution - 0069

Pittsburgh, Pennsylvania, United States

Site Status

Local Institution - 0154

Greenville, South Carolina, United States

Site Status

Local Institution - 0062

Nashville, Tennessee, United States

Site Status

Local Institution - 0064

Nashville, Tennessee, United States

Site Status

Local Institution - 0044

Dallas, Texas, United States

Site Status

Texas Oncology

Dallas, Texas, United States

Site Status

Local Institution - 0088

Houston, Texas, United States

Site Status

Local Institution - 0089

Salt Lake City, Utah, United States

Site Status

Local Institution - 0054

Seattle, Washington, United States

Site Status

Local Institution - 0017

Camperdown, New South Wales, Australia

Site Status

Local Institution - 0031

Coffs Harbour, New South Wales, Australia

Site Status

Local Institution - 0028

Gateshead, New South Wales, Australia

Site Status

Local Institution - 0023

Macquarie University, New South Wales, Australia

Site Status

Local Institution - 0138

North Sydney, New South Wales, Australia

Site Status

Local Institution - 0019

Brisbane, Queensland, Australia

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Local Institution - 0022

Southport, Queensland, Australia

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Local Institution - 0018

Woolloongabba, Queensland, Australia

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Local Institution - 0020

Adelaide, South Australia, Australia

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Local Institution - 0025

Kurralta Park, South Australia, Australia

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Local Institution - 0024

Box Hill, Victoria, Australia

Site Status

Local Institution - 0016

Heidelberg, Victoria, Australia

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Local Institution - 0026

Melbourne, Victoria, Australia

Site Status

Local Institution - 0021

Nedlands, Western Australia, Australia

Site Status

Local Institution - 0148

Salzburg, , Austria

Site Status

Local Institution - 0145

Vienna, , Austria

Site Status

Local Institution - 0003

Brussels, , Belgium

Site Status

Local Institution - 0002

Brussels, , Belgium

Site Status

Local Institution - 0004

Edegem, , Belgium

Site Status

Local Institution - 0005

Ghent, , Belgium

Site Status

Local Institution - 0103

Leuven, , Belgium

Site Status

Local Institution - 0140

Edmonton, Alberta, Canada

Site Status

Local Institution - 0165

Vancouver, British Columbia, Canada

Site Status

Local Institution - 0141

London, Ontario, Canada

Site Status

Local Institution - 0143

Ottawa, Ontario, Canada

Site Status

Local Institution - 0166

Toronto, Ontario, Canada

Site Status

Local Institution - 0139

Montreal, Quebec, Canada

Site Status

Local Institution - 0142

Québec, Quebec, Canada

Site Status

Local Institution - 0092

Brno, , Czechia

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Local Institution - 0091

Hradec Králové, , Czechia

Site Status

Local Institution - 0090

Prague, , Czechia

Site Status

Local Institution - 0167

Prague, , Czechia

Site Status

Local Institution - 0076

Aarhus, , Denmark

Site Status

Local Institution - 0078

Herlev, , Denmark

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Local Institution - 0077

Odense, , Denmark

Site Status

Local Institution - 0071

Helsinki, Uusimaa, Finland

Site Status

Local Institution - 0169

Tampere, , Finland

Site Status

Local Institution - 0125

Boulogne-Billancourt, , France

Site Status

Local Institution - 0126

Marseille, , France

Site Status

Local Institution - 0056

Nantes, , France

Site Status

Local Institution - 0058

Paris, , France

Site Status

Local Institution - 0124

Pierre-Bénite, , France

Site Status

Local Institution - 0127

Rennes, , France

Site Status

Local Institution

Villejuif, , France

Site Status

Local Institution - 0162

Buxtehude, , Germany

Site Status

Local Institution - 0161

Erfurt, , Germany

Site Status

Local Institution - 0171

Erlangen, , Germany

Site Status

Local Institution - 0156

Essen, , Germany

Site Status

Local Institution - 0159

Hanover, , Germany

Site Status

Local Institution - 0157

Heidelberg, , Germany

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Local Institution - 0158

Kiel, , Germany

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Local Institution - 0178

Leipzig, , Germany

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Local Institution - 0160

München, , Germany

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Local Institution - 0134

Tübingen, , Germany

Site Status

Local Institution - 0035

Dublin, Dublin, Ireland

Site Status

Local Institution - 0033

Cork, , Ireland

Site Status

Local Institution - 0168

Dublin, , Ireland

Site Status

Local Institution - 0036

Dublin, , Ireland

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Local Institution - 0034

Dublin, , Ireland

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Local Institution - 0032

Galway, , Ireland

Site Status

Local Institution - 0120

Jerusalem, , Israel

Site Status

Local Institution - 0121

Tel Litwinsky, , Israel

Site Status

Local Institution - 0176

Bergamo, , Italy

Site Status

Local Institution - 0115

Genova, , Italy

Site Status

Local Institution - 0113

Meldola (FC), , Italy

Site Status

Local Institution - 0172

Milan, , Italy

Site Status

Local Institution - 0117

Milan, , Italy

Site Status

Local Institution - 0114

Napoli, , Italy

Site Status

Local Institution - 0118

Padua, , Italy

Site Status

Local Institution - 0177

Roma, , Italy

Site Status

Local Institution - 0116

Siena, , Italy

Site Status

Local Institution - 0010

Amsterdam, , Netherlands

Site Status

Local Institution - 0012

Leiden, , Netherlands

Site Status

Local Institution - 0013

Nijmegen, , Netherlands

Site Status

Local Institution - 0029

Auckland, , New Zealand

Site Status

Local Institution - 0123

Oslo, , Norway

Site Status

Local Institution - 0109

Gdansk, , Poland

Site Status

Local Institution - 0133

Krakow, , Poland

Site Status

Local Institution - 0060

Lodz, , Poland

Site Status

Local Institution - 0059

Warsaw, , Poland

Site Status

Local Institution - 0130

Moscow, , Russia

Site Status

Local Institution - 0132

Saint Petersburg, , Russia

Site Status

Local Institution - 0128

Saint Petersburg, , Russia

Site Status

Local Institution - 0131

Samara, , Russia

Site Status

Local Institution - 0152

Badalona-Barcelona, , Spain

Site Status

Local Institution - 0151

Barcelona, , Spain

Site Status

Local Institution - 0175

Barcelona, , Spain

Site Status

Local Institution - 0150

Madrid, , Spain

Site Status

Local Institution - 0149

Madrid, , Spain

Site Status

Local Institution - 0153

Málaga, , Spain

Site Status

Local Institution - 0147

Pamplona, , Spain

Site Status

Local Institution - 0182

Gothenberg, , Sweden

Site Status

Local Institution - 0184

Stockholm, , Sweden

Site Status

Local Institution - 0164

Geneva, , Switzerland

Site Status

Local Institution - 0189

Lausanne, , Switzerland

Site Status

Local Institution - 0186

Sankt Gallen, , Switzerland

Site Status

Local Institution - 0163

Zurich, , Switzerland

Site Status

Local Institution - 0039

Glasgow, Dumfries & Galloway, United Kingdom

Site Status

Local Institution - 0038

London, Greater London, United Kingdom

Site Status

Local Institution - 0119

Manchester, Greater Manchester, United Kingdom

Site Status

Local Institution - 0041

Northwood, Middlesex, United Kingdom

Site Status

Local Institution - 0122

Nottingham, Nottinghamshire, United Kingdom

Site Status

Local Institution - 0037

Cambridge, , United Kingdom

Site Status

Local Institution - 0040

Swansea, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada Czechia Denmark Finland France Germany Ireland Israel Italy Netherlands New Zealand Norway Poland Russia Spain Sweden Switzerland United Kingdom

References

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Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.

Reference Type DERIVED
PMID: 39504507 (View on PubMed)

Wolchok JD, Chiarion-Sileni V, Rutkowski P, Cowey CL, Schadendorf D, Wagstaff J, Queirolo P, Dummer R, Butler MO, Hill AG, Postow MA, Gaudy-Marqueste C, Medina T, Lao CD, Walker J, Marquez-Rodas I, Haanen JBAG, Guidoboni M, Maio M, Schoffski P, Carlino MS, Sandhu S, Lebbe C, Ascierto PA, Long GV, Ritchings C, Nassar A, Askelson M, Benito MP, Wang W, Hodi FS, Larkin J; CheckMate 067 Investigators. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025 Jan 2;392(1):11-22. doi: 10.1056/NEJMoa2407417. Epub 2024 Sep 15.

Reference Type DERIVED
PMID: 39282897 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34855329 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34818112 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31562797 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30361170 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28889792 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28662232 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28651159 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26027431 (View on PubMed)

Related Links

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Other Identifiers

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2012-005371-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-067

Identifier Type: -

Identifier Source: org_study_id

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