Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma

NCT02388906 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-2382014-002351-26
• Study Type: interventional
• Target: 906
• Locations: 24 countries
• Sites: 134

Brief Summary

The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Recurrence-free Survival (RFS)

  RFS is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.

  up to 36 months

Secondary Outcomes (7)

• Overall Survival (OS)

  up to 106.6 months

• The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events

  reported between first dose and 30 days after last dose of study therapy

• The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Serious Adverse Events

  reported between the first dose and 30 days after last dose of study therapy

• the Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Deaths

  reported between first dose and 30 to 100 days after last dose of study therapy

• The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Laboratory Abnormalities

  reported after first dose and within 30 days of last dose of the study therapy

Study Arms (2)

Ipilimumab and Placebo matching Nivolumab

EXPERIMENTAL

Drug: Ipilimumab; Other: Placebo matching Nivolumab

Nivolumab and Placebo matching Ipilimumab

EXPERIMENTAL

Drug: Nivolumab; Other: Placebo matching Ipilimumab

Interventions

Ipilimumab DRUG

Specified dose on specified days

Ipilimumab and Placebo matching Nivolumab

Nivolumab DRUG

Specified dose on specified days

Nivolumab and Placebo matching Ipilimumab

Placebo matching Ipilimumab OTHER

Specified dose on specified days

Nivolumab and Placebo matching Ipilimumab

Placebo matching Nivolumab OTHER

Specified dose on specified days

Ipilimumab and Placebo matching Nivolumab

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 15 years of age Except: where local regulations and/or institutional policies do not allow for subjects \< 18 years of age (pediatric population) to participate. For those sites, the eligible subject population is ≥ 18 years of age
• Completely removed melanoma by surgery performed within 12 weeks of randomization
• Stage IIIb/C or Stage IV before complete resection
• No previous anti-cancer treatment

You may not qualify if:

• Ocular or uveal melanoma
• History of carcinomatosis meningitis
• History of auto-immune disease
• Treatment directed against the resected melanoma that is administrated after the surgery

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (136)

Local Institution - 0036

Little Rock, Arkansas, 72205, United States

Location

Local Institution - 0117

La Jolla, California, 92093-0698, United States

Location

Local Institution - 0189

Los Angeles, California, 90025, United States

Location

Local Institution - 0021

San Francisco, California, 94109, United States

Location

Local Institution - 0006

San Francisco, California, 94143, United States

Location

Local Institution - 0010

Aurora, Colorado, 80045, United States

Location

Local Institution - 0004

Washington D.C., District of Columbia, 20007, United States

Location

Local Institution - 0012

Jacksonville, Florida, 32207, United States

Location

Local Institution - 0019

Miami Beach, Florida, 33140, United States

Location

Local Institution - 0030

Orlando, Florida, 32806, United States

Location

Local Institution - 0032

Tampa, Florida, 33612, United States

Location

Local Institution - 0016

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0106

Chicago, Illinois, 60637, United States

Location

Local Institution - 0013

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0170

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0171

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0015

Ann Arbor, Michigan, 48109-5869, United States

Location

Local Institution - 0002

Robbinsdale, Minnesota, 55407, United States

Location

Local Institution - 0017

St Louis, Missouri, 63110, United States

Location

Local Institution - 0123

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0095

New Brunswick, New Jersey, 08903, United States

Location

Local Institution - 0024

New York, New York, 10016, United States

Location

Local Institution - 0033

New York, New York, 10065, United States

Location

Local Institution - 0003

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0025

Durham, North Carolina, 27710, United States

Location

Local Institution - 0157

Columbus, Ohio, 43210, United States

Location

Local Institution - 0031

Portland, Oregon, 97213, United States

Location

Local Institution - 0029

Portland, Oregon, 97239, United States

Location

Local Institution - 0022

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0001

Bethlehem, Pennsylvania, 18015, United States

Location

Local Institution - 0026

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0014

Nashville, Tennessee, 37203-1624, United States

Location

Local Institution - 0005

Dallas, Texas, 75246, United States

Location

Local Institution - 0027

Charlottesville, Virginia, 22908, United States

Location

Local Institution - 0126

Seattle, Washington, 98109, United States

Location

Local Institution - 0142

Capital Federal, Buenos Aires, 1426, Argentina

Location

Local Institution - 0140

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Local Institution

Córdoba, 5000, Argentina

Location

Local Institution - 0079

Gateshead, New South Wales, 2290, Australia

Location

Local Institution - 0080

Westmead, New South Wales, 2145, Australia

Location

Local Institution - 0078

Wollstonecraft, New South Wales, 2065, Australia

Location

Local Institution - 0082

Greenslopes, Queensland, 4120, Australia

Location

Local Institution - 0083

Southport, Queensland, 4215, Australia

Location

Local Institution - 0084

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 0075

Heidelberg, Victoria, 3084, Australia

Location

Local Institution - 0077

Prahran, Victoria, 3181, Australia

Location

Local Institution - 0085

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0081

Camperdown, 2050, Australia

Location

Local Institution - 0169

Graz, 8036, Austria

Location

Local Institution - 0168

Salzburg, 5020, Austria

Location

Local Institution - 0038

Brussels, 1090, Belgium

Location

Local Institution - 0040

Brussels, 1200, Belgium

Location

Local Institution - 0037

Ghent, 9000, Belgium

Location

Local Institution - 0039

Leuven, 3000, Belgium

Location

Local Institution - 0051

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0074

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0094

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0105

Montreal, Quebec, H3T 1E2, Canada

Location

Local Institution - 0046

Québec, Quebec, G1J 1Z4, Canada

Location

Local Institution - 0101

Hradec Králové, 500 05, Czechia

Location

Local Institution - 0102

Ostrava-Poruba, 708 52, Czechia

Location

Local Institution - 0099

Prague, 110 00, Czechia

Location

Local Institution - 0100

Prague, 128 08, Czechia

Location

Local Institution - 0047

Helsinki, 00029, Finland

Location

Local Institution - 0048

Tampere, 33521, Finland

Location

Local Institution - 0138

Lille, 59037, France

Location

Local Institution - 0135

Marseille, 13385, France

Location

Local Institution - 0134

Nantes, 44000, France

Location

Local Institution - 0136

Paris, 75010, France

Location

Local Institution - 0133

Pierre-Bénite, 69495, France

Location

Local Institution - 0137

Toulouse, 31059, France

Location

Local Institution - 0086

Athens, 11526, Greece

Location

Local Institution - 0087

Neo Faliro, 18547, Greece

Location

Local Institution - 0163

Budapest, 1122, Hungary

Location

Local Institution - 0063

Dublin, 01, Ireland

Location

Local Institution - 0166

Dublin, 0, Ireland

Location

Local Institution - 0108

Dublin, 4, Ireland

Location

Local Institution - 0064

Galway, Ireland

Location

Local Institution - 0112

Bergamo, 24127, Italy

Location

Local Institution - 0116

Genova, 16128, Italy

Location

Local Institution - 0115

Meldola (FC), 47014, Italy

Location

Local Institution - 0113

Milan, 20133, Italy

Location

Local Institution - 0107

Napoli, 80131, Italy

Location

Local Institution - 0111

Padua, Padova, Italy

Location

Local Institution - 0114

Roma, 00144, Italy

Location

Local Institution - 0110

Siena, 53100, Italy

Location

Local Institution - 0179

Nagoya, Aichi-ken, 466-8560, Japan

Location

Local Institution - 0161

Fukuoka, Fukuoka, 8128582, Japan

Location

Local Institution - 0174

Tsukuba, Ibaraki, 3058576, Japan

Location

Local Institution - 0162

Kumamoto, Kumamoto, 8608556, Japan

Location

Local Institution - 0160

Matsumoto, Nagano, 3908621, Japan

Location

Local Institution - 0175

Niigata, Niigata, 9518566, Japan

Location

Local Institution - 0176

Osaka, Osaka, 5400006, Japan

Location

Local Institution - 0159

Sunto-gun, Shizuoka, 4118777, Japan

Location

Local Institution - 0158

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0180

Chuo-shi, Yamanashi, 4093898, Japan

Location

Local Institution - 0042

Amsterdam, 1081 HV, Netherlands

Location

Local Institution - 0045

Groningen, 9713 GZ, Netherlands

Location

Local Institution - 0043

Nijmegen, 6525GA, Netherlands

Location

Local Institution - 0041

Veldhoven, 5504 DB, Netherlands

Location

Local Institution - 0098

Bergen, 5021, Norway

Location

Local Institution - 0109

Oslo, 3100, Norway

Location

Local Institution - 0150

Gdansk, 80-219, Poland

Location

Local Institution - 0149

Krakow, 31-115, Poland

Location

Local Institution - 0152

Warsaw, 02-781, Poland

Location

Local Institution - 0156

Craiova, 200542, Romania

Location

Local Institution - 0153

Romania, 400015, Romania

Location

Local Institution - 0148

Johannesburg, Gauteng, 2196, South Africa

Location

Local Institution - 0145

Pretoria, Gauteng, 0075, South Africa

Location

Local Institution - 0147

Saxonwold, Johannesburg, Gauteng, 2196, South Africa

Location

Local Institution - 0181

Cape Town, Western Cape, 7700, South Africa

Location

Local Institution - 0146

Kraaifontein, Western Cape, 7570, South Africa

Location

Local Institution - 0144

Songpa-gu, Seoul, 05505, South Korea

Location

Local Institution - 0129

Seoul, 03080, South Korea

Location

Local Institution - 0127

Seoul, 03722, South Korea

Location

Local Institution - 0128

Seoul, 06351, South Korea

Location

Local Institution - 0120

Barcelona, 08036, Spain

Location

Local Institution - 0119

Madrid, 28007, Spain

Location

Local Institution - 0121

Seville, 41009, Spain

Location

Local Institution - 0122

Valencia, 46014, Spain

Location

Local Institution - 0050

Gothenberg, 413 45, Sweden

Location

Local Institution - 0096

Lund, 221 85, Sweden

Location

Local Institution - 0167

Zurich, 8091, Switzerland

Location

Local Institution - 0131

Kaohsiung City, 833, Taiwan

Location

Local Institution - 0132

Taichung, 404, Taiwan

Location

Local Institution - 0130

Taoyuan District, 333, Taiwan

Location

Local Institution - 0057

Bristol, Avon, BS2 8ED, United Kingdom

Location

Local Institution - 0052

Swansea, Carmarthenshire, SA2 8QA, United Kingdom

Location

Local Institution - 0165

London, Greater London, SW3 6JJ, United Kingdom

Location

Local Institution - 0054

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0056

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Local Institution - 0177

Northwood, Middlesex, HA6 2JR, United Kingdom

Location

Local Institution - 0055

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Local Institution - 0060

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Local Institution - 0097

Leicester, LE15WW, United Kingdom

Location

Local Institution - 0053

Surrey, SM2 5PT, United Kingdom

Location

Related Publications (8)

• Ascierto PA, Del Vecchio M, Merelli B, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Gaudy-Marqueste C, Pigozzo J, Marquez-Rodas I, Butler MO, Di Giacomo AM, Gligich O, De La Cruz-Merino L, Arenberger P, Atkinson V, Nathan P, Hill A, Millward M, Fecher LA, Khushalani NI, Queirolo P, Soomro R, Rathod D, Askelson M, Pe Benito M, Joseph D, Larkin J. Nivolumab for Resected Stage III or IV Melanoma at 9 Years. N Engl J Med. 2025 Oct 18. doi: 10.1056/NEJMoa2504966. Online ahead of print.

  PMID: 41124198 DERIVED

• Weber JS, Middleton MR, Yates G, Sharpe DJ, Kurt M, Lobo M, Moshyk A, Vanderpuye-Orgle J, Mohr P. Estimating Long-Term Survivorship Rates Among Patients With Resected Stage III/IV Melanoma: Analyses From CheckMate 238 and European Organization for Research and Treatment of Cancer 18071 Trials. J Clin Oncol. 2025 Mar 10;43(8):929-937. doi: 10.1200/JCO.24.00237. Epub 2024 Oct 8.

  PMID: 39378385 DERIVED

• Weber J, Del Vecchio M, Mandala M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, de la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Long GV, Lobo M, Askelson M, Ascierto PA, Larkin J. Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238. J Clin Oncol. 2024 Nov;42(31):3702-3712. doi: 10.1200/JCO.23.01448. Epub 2024 Aug 5.

  PMID: 39102624 DERIVED

• Larkin J, Weber J, Del Vecchio M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, Middleton MR, De la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Long GV, Lobo M, Askelson M, Ascierto PA, Mandala M. Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria. Eur J Cancer. 2022 Sep;173:285-296. doi: 10.1016/j.ejca.2022.06.041. Epub 2022 Aug 11.

  PMID: 35964471 DERIVED

• Weber JS, Ascierto PA, Middleton MR, Hennicken D, Zoffoli R, Pieters A, Amadi A, Kupas K, Kotapati S, Moshyk A, Schadendorf D. Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma. Eur J Cancer. 2021 Nov;158:225-233. doi: 10.1016/j.ejca.2021.08.028. Epub 2021 Oct 15.

  PMID: 34663559 DERIVED

• Mandala M, Larkin J, Ascierto PA, Del Vecchio M, Gogas H, Cowey CL, Arance A, Dalle S, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Di Giacomo AM, Lutzky J, De La Cruz-Merino L, Atkinson V, Arenberger P, Hill A, Fecher L, Millward M, Khushalani NI, de Pril V, Lobo M, Weber J. Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. J Immunother Cancer. 2021 Aug;9(8):e003188. doi: 10.1136/jitc-2021-003188.

  PMID: 34452930 DERIVED

• Ascierto PA, Del Vecchio M, Mandala M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, Marquez-Rodas I, Butler MO, Maio M, Middleton MR, de la Cruz-Merino L, Arenberger P, Atkinson V, Hill A, Fecher LA, Millward M, Khushalani NI, Queirolo P, Lobo M, de Pril V, Loffredo J, Larkin J, Weber J. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1465-1477. doi: 10.1016/S1470-2045(20)30494-0. Epub 2020 Sep 19.

  PMID: 32961119 DERIVED

• Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, Dalle S, Schenker M, Chiarion-Sileni V, Marquez-Rodas I, Grob JJ, Butler MO, Middleton MR, Maio M, Atkinson V, Queirolo P, Gonzalez R, Kudchadkar RR, Smylie M, Meyer N, Mortier L, Atkins MB, Long GV, Bhatia S, Lebbe C, Rutkowski P, Yokota K, Yamazaki N, Kim TM, de Pril V, Sabater J, Qureshi A, Larkin J, Ascierto PA; CheckMate 238 Collaborators. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017 Nov 9;377(19):1824-1835. doi: 10.1056/NEJMoa1709030. Epub 2017 Sep 10.

  PMID: 28891423 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 17, 2015
• Study Start: March 16, 2015
• Primary Completion: November 26, 2018
• Study Completion: October 16, 2024
• Last Updated: April 24, 2025
• Results First Posted: June 15, 2021

Record last verified: 2025-04

Locations

ZA (5); KR (4); ES (4); SE (2); AU (10); IE (4); TW (3); HU (1); CH (1); BE (4); JP (10); PL (3); FR (6); FI (2); RO (2); GB (10); US (35); CA (5); CZ (4); AR (3); GR (2); IT (8); NL (4); NO (2)