MelanomaPhase 3CheckMate 238NCT02388906
Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIb/c or Stage IV Melanoma
A Phase 3 study testing Ipilimumab and Nivolumab in people with Melanoma, run by Bristol-Myers Squibb at 136 sites in 25 countries.
Trial summary
The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Ipilimumab and Nivolumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 906 participants
- Where
- 136 sitesin 25 countries
- Study dates
- 16 Mar 2015to 16 Oct 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
- Other protocol-defined inclusion/exclusion criteria apply
Trial locations and contacts
136 sites in 25 countries.
136 sites in 25 countries
United States35 sites
Local Institution - 0022
Allentown, Pennsylvania, 18103
Local Institution - 0015
Ann Arbor, Michigan, 48109-5869
Local Institution - 0016
Atlanta, Georgia, 30322
Local Institution - 0010
Aurora, Colorado, 80045
Local Institution - 0001
Bethlehem, Pennsylvania, 18015
Local Institution - 0013
Boston, Massachusetts, 02215
Local Institution - 0170
Boston, Massachusetts, 02215
Local Institution - 0171
Boston, Massachusetts, 02215
Local Institution - 0026
Charleston, South Carolina, 29425
Local Institution - 0003
Charlotte, North Carolina, 28204
Local Institution - 0027
Charlottesville, Virginia, 22908
Local Institution - 0106
Chicago, Illinois, 60637
Local Institution - 0157
Columbus, Ohio, 43210
Local Institution - 0005
Dallas, Texas, 75246
Local Institution - 0025
Durham, North Carolina, 27710
Local Institution - 0123
Hackensack, New Jersey, 07601
Local Institution - 0012
Jacksonville, Florida, 32207
Local Institution - 0117
La Jolla, California, 92093-0698
Local Institution - 0036
Little Rock, Arkansas, 72205
Local Institution - 0189
Los Angeles, California, 90025
Local Institution - 0019
Miami Beach, Florida, 33140
Local Institution - 0014
Nashville, Tennessee, 37203-1624
Local Institution - 0095
New Brunswick, New Jersey, 08903
Local Institution - 0024
New York, New York, 10016
Local Institution - 0033
New York, New York, 10065
Local Institution - 0030
Orlando, Florida, 32806
Local Institution - 0031
Portland, Oregon, 97213
Local Institution - 0029
Portland, Oregon, 97239
Local Institution - 0002
Robbinsdale, Minnesota, 55407
Local Institution - 0021
San Francisco, California, 94109
Local Institution - 0006
San Francisco, California, 94143
Local Institution - 0126
Seattle, Washington, 98109
Local Institution - 0017
St Louis, Missouri, 63110
Local Institution - 0032
Tampa, Florida, 33612
Local Institution - 0004
Washington D.C., District of Columbia, 20007
Australia10 sites
Local Institution - 0084
Adelaide, South Australia, 5000
Local Institution - 0081
Camperdown, 2050
Local Institution - 0079
Gateshead, New South Wales, 2290
Local Institution - 0082
Greenslopes, Queensland, 4120
Local Institution - 0075
Heidelberg, Victoria, 3084
Local Institution - 0085
Nedlands, Western Australia, 6009
Local Institution - 0077
Prahran, Victoria, 3181
Local Institution - 0083
Southport, Queensland, 4215
Local Institution - 0080
Westmead, New South Wales, 2145
Local Institution - 0078
Wollstonecraft, New South Wales, 2065
Japan10 sites
Local Institution - 0158
Chuo-ku, Tokyo, 1040045
Local Institution - 0180
Chuo-shi, Yamanashi, 4093898
Local Institution - 0161
Fukuoka, Fukuoka, 8128582
Local Institution - 0162
Kumamoto, Kumamoto, 8608556
Local Institution - 0160
Matsumoto, Nagano, 3908621
Local Institution - 0179
Nagoya, Aichi-ken, 466-8560
Local Institution - 0175
Niigata, Niigata, 9518566
Local Institution - 0176
Osaka, Osaka, 5400006
Local Institution - 0159
Sunto-gun, Shizuoka, 4118777
Local Institution - 0174
Tsukuba, Ibaraki, 3058576
United Kingdom10 sites
Local Institution - 0057
Bristol, Avon, BS2 8ED
Local Institution - 0097
Leicester, LE15WW
Local Institution - 0165
London, Greater London, SW3 6JJ
Local Institution - 0054
Manchester, Greater Manchester, M20 4BX
Local Institution - 0060
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
Local Institution - 0177
Northwood, Middlesex, HA6 2JR
Local Institution - 0055
Oxford, Oxfordshire, OX3 7LJ
Local Institution - 0056
Southampton, Hampshire, SO16 6YD
Local Institution - 0053
Surrey, SM2 5PT
Local Institution - 0052
Swansea, Carmarthenshire, SA2 8QA
Italy8 sites
Local Institution - 0112
Bergamo, 24127
Local Institution - 0116
Genova, 16128
Local Institution - 0115
Meldola (FC), 47014
Local Institution - 0113
Milan, 20133
Local Institution - 0107
Naples, 80131
Local Institution - 0111
Padova, Padova
Local Institution - 0114
Roma, 00144
Local Institution - 0110
Siena, 53100
France6 sites
Local Institution - 0138
Lille, 59037
Local Institution - 0135
Marseille, 13385
Local Institution - 0134
Nantes, 44000
Local Institution - 0136
Paris, 75010
Local Institution - 0133
Pierre-Bénite, 69495
Local Institution - 0137
Toulouse, 31059
Canada5 sites
Local Institution - 0051
Edmonton, Alberta, T6G 1Z2
Local Institution - 0105
Montreal, Quebec, H3T 1E2
Local Institution - 0046
Québec, Quebec, G1J 1Z4
Local Institution - 0094
Toronto, Ontario, M5G 2M9
Local Institution - 0074
Vancouver, British Columbia, V5Z 4E6
South Africa5 sites
Local Institution - 0181
Cape Town, Western Cape, 7700
Local Institution - 0148
Johannesburg, Gauteng, 2196
Local Institution - 0146
Kraaifontein, Western Cape, 7570
Local Institution - 0145
Pretoria, Gauteng, 0075
Local Institution - 0147
Saxonwold, Johannesburg, Gauteng, 2196
Belgium4 sites
Local Institution - 0038
Brussels, 1090
Local Institution - 0040
Brussels, 1200
Local Institution - 0037
Ghent, 9000
Local Institution - 0039
Leuven, 3000
Czechia4 sites
Local Institution - 0101
Hradec Králové, 500 05
Local Institution - 0102
Ostrava-Poruba, 708 52
Local Institution - 0099
Prague, 110 00
Local Institution - 0100
Prague, 128 08
Ireland4 sites
Local Institution - 0063
Dublin, 01
Local Institution - 0166
Dublin, 0
Local Institution - 0108
Dublin, 4
Local Institution - 0064
Galway
Netherlands4 sites
Local Institution - 0042
Amsterdam, 1081 HV
Local Institution - 0045
Groningen, 9713 GZ
Local Institution - 0043
Nijmegen, 6525GA
Local Institution - 0041
Veldhoven, 5504 DB
South Korea4 sites
Local Institution - 0129
Seoul, 03080
Local Institution - 0127
Seoul, 03722
Local Institution - 0128
Seoul, 06351
Local Institution - 0144
Songpa-gu, Seoul, 05505
Spain4 sites
Local Institution - 0120
Barcelona, 08036
Local Institution - 0119
Madrid, 28007
Local Institution - 0121
Seville, 41009
Local Institution - 0122
Valencia, 46014
Argentina3 sites
Local Institution - 0142
Capital Federal, Buenos Aires, 1426
Local Institution
Córdoba, 5000
Local Institution - 0140
San Miguel de Tucumán, Tucumán Province, 4000
Poland3 sites
Local Institution - 0150
Gdansk, 80-219
Local Institution - 0149
Krakow, 31-115
Local Institution - 0152
Warsaw, 02-781
Taiwan3 sites
Local Institution - 0131
Kaohsiung City, 833
Local Institution - 0132
Taichung, 404
Local Institution - 0130
Taoyuan, 333
Austria2 sites
Local Institution - 0169
Graz, 8036
Local Institution - 0168
Salzburg, 5020
Finland2 sites
Local Institution - 0047
Helsinki, 00029
Local Institution - 0048
Tampere, 33521
Greece2 sites
Local Institution - 0086
Athens, 11526
Local Institution - 0087
Neo Faliro, 18547
Norway2 sites
Local Institution - 0098
Bergen, 5021
Local Institution - 0109
Oslo, 3100
Romania2 sites
Local Institution - 0156
Craiova, 200542
Local Institution - 0153
Romania, 400015
Sweden2 sites
Local Institution - 0050
Gothenberg, 413 45
Local Institution - 0096
Lund, 221 85
About this study
Official title: A Phase 3, Randomized, Double-blind Study of Adjuvant Immunotherapy With Nivolumab Versus Ipilimumab After Complete Resection of Stage IIIb/c or Stage IV Melanoma in Subjects Who Are at High Risk for Recurrence (CheckMate 238: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 238)
The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.
- Conditions
- Melanoma
- Being tested
- Ipilimumab, Nivolumab, Placebo matching Ipilimumab, Placebo matching Nivolumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Specified dose on specified days
NivolumabDrug
Specified dose on specified days
Placebo matching IpilimumabOther
Specified dose on specified days
Placebo matching NivolumabOther
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab and Placebo matching Nivolumab | Experimental | Not described Receives: Drug: Ipilimumab; Other: Placebo matching Nivolumab |
| Nivolumab and Placebo matching Ipilimumab | Experimental | Not described Receives: Drug: Nivolumab; Other: Placebo matching Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 36 months
Secondary outcomes (7)
Overall Survival (OS)
OS is defined as as the time between the date of randomization and the date of death.
Measured: up to 106.6 months
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of adverse events
Measured: 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
The Safety and Tolerability of nivolumab and ipilimumab was measured by the incidence of serious adverse events
Measured: 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
the safety and tolerability of Nivolumab and Ipilimumab was measured by the incidence of Deaths
Measured: 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
The Safety and Tolerability of Nivolumab and Ipilimumab measured by the incidence of Laboratory abnormalities.
Measured: reported after first dose and within 30 days of last dose of the study therapy
Recurrence-free Survival by PD-L1 Expression
Recurrence-free survival by PD-L1 Expression(5% tumor cell membrane expression)
Measured: up to 106.6 months
Health Related Quality of Life (HRQoL) Evaluation
HRQoL was measured by mean changes from baseline in EORTC-QLQ-C30 global health status/QoL composite scale and in remaining EORTC QLQ-C30 scales in all randomized participants.
EORTC QLQ-C30 is the most commonly used QoL instrument in melanoma clinical studies, is a 30-item instrument that has gained wide acceptance in oncology clinical studies and comprises 5 functional scales (physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Except for the overall health status and global quality of life items, responses for all items are 4 point categorical scales ranging from 1 (Not at all) to 4 (Very much). The overall health status/quality of life responses are 7-point Likert scales for which higher score reflects higher health status/quality of life for the 7-point Likert scale.
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study start16 Mar 2015
- Primary completion26 Nov 2018
- Study completion16 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 906 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02388906
- Sponsor's protocol ID
- CA209-238
- Other IDs
- 2014-002351-26, 2014
- Acronym
- CheckMate 238
- Status last verified
- Apr 2025
- First submitted
- 10 Mar 2015
- Last updated
- 24 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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. 2026 Jan 22;394(4):333-342. doi: 10.1056/NEJMoa2504966. Epub 2025 Oct 18.
PubMed 41124198Weber 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.
PubMed 39378385Weber 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.
PubMed 39102624Larkin 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.
PubMed 35964471Weber 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.
PubMed 34663559Mandala 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.
PubMed 34452930Ascierto 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.
PubMed 32961119Weber 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.
PubMed 28891423
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-blind Study of Adjuvant Immunotherapy With Nivolumab Versus Ipilimumab After Complete Resection of Stage IIIb/c or Stage IV Melanoma in Subjects Who Are at High Risk for Recurrence (CheckMate 238: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 238)
- ClinicalTrials.gov ID
- NCT02388906
- Acronym / sponsor ID
- CheckMate 238 / CA209-238
- Conditions
- Melanoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 906 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Study start
- 16 Mar 2015 (actual)
- Primary completion
- 26 Nov 2018 (actual)
- Study completion
- 16 Oct 2024 (actual)
- First posted
- 17 Mar 2015 (estimated)
- Results
- Posted 15 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether nivolumab is better than ipilimumab to prevent recurrence of melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab and Placebo matching Nivolumab | Experimental | Drug: Ipilimumab, Other: Placebo matching Nivolumab |
| Nivolumab and Placebo matching Ipilimumab | Experimental | Drug: Nivolumab, Other: Placebo matching Ipilimumab |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
- Other protocol-defined inclusion/exclusion criteria apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabSpecified dose on specified days | Drug | Ipilimumab and Placebo matching Nivolumab |
| NivolumabSpecified dose on specified days | Drug | Nivolumab and Placebo matching Ipilimumab |
| Placebo matching IpilimumabSpecified dose on specified days | Other | Nivolumab and Placebo matching Ipilimumab |
| Placebo matching NivolumabSpecified dose on specified days | Other | Ipilimumab and Placebo matching Nivolumab |
Primary outcome
Recurrence-free Survival (RFS)
Time frame: up to 36 months
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.
7 secondary outcomes
Overall Survival (OS)
Time frame: up to 106.6 months
The Safety and Tolerability of Nivolumab and Ipilimumab Measured by the Incidence of Adverse Events
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: reported after first dose and within 30 days of last dose of the study therapy
Recurrence-free Survival by PD-L1 Expression
Time frame: up to 106.6 months
Health Related Quality of Life (HRQoL) Evaluation
Time frame: up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41124198Ascierto 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. 2026 Jan 22;394(4):333-342. doi: 10.1056/NEJMoa2504966. Epub 2025 Oct 18.
- Derived from this study: PubMed 39378385Weber 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.
- Derived from this study: PubMed 39102624Weber 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.
- Derived from this study: PubMed 35964471Larkin 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.
- Derived from this study: PubMed 34663559Weber 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.
- Derived from this study: PubMed 34452930Mandala 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.
- Derived from this study: PubMed 32961119Ascierto 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.
- Derived from this study: PubMed 28891423Weber 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.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
136 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ipilimumab and Nivolumab in people with Melanoma, run by Bristol-Myers Squibb at 136 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 136 sites in United States, Australia, Japan, United Kingdom, Italy and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence-free Survival (RFS) (time frame: up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02388906, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.