MelanomaPhase 3NCT02362594
Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/1325-MG/KEYNOTE-054)
A Phase 3 study testing pembrolizumab in people with Melanoma, run by Merck Sharp & Dohme LLC.
Trial summary
This study will assess whether post-surgery therapy with pembrolizumab improves recurrence-free survival (RFS) as compared to placebo for high-risk participants with melanoma (Stage IIIA [> 1 mm metastasis], IIIB and IIIC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,019 participants
- Where
- No sites listed yet
- Study dates
- 16 Jul 2015to 1 Nov 2026
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completely resected Stage III melanoma
- Tumor tissue available for evaluation of PD-L1 expression
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
- No prior therapy for melanoma except surgery for primary melanoma lesions (or previously treated with interferon for thick primary melanomas without evidence of lymph node involvement are eligible)
- Female participants of childbearing potential should be willing to use adequate methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
- Male participants should agree to use an adequate method of birth control starting with the first dose of study therapy through 120 days after the last dose of study medication
Who cannot join
- Mucosal or ocular melanoma
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- History of or current interstitial lung disease
- History of hematologic or primary solid tumor malignancy, unless no evidence of that disease for 5 years
- Active autoimmune disease that has required systemic treatment in past 2 years
- Active infection requiring therapy
Show all 15Show fewer
- Unstable hyperthyroidism or hypothyroidism
- Diagnosis of immunodeficiency
- Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
- Known history of human immunodeficiency virus (HIV), active Hepatitis B or C
- Treatment with live vaccine within 30 days prior to the first dose of study medication are not eligible
- Prior treatment with any anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody or anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent, or prior participation in any Merck pembrolizumab clinical trial
- Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study medication
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study medication
- Participant is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial without prospective Institutional Review Board approval (by chair or designee) is given
About this study
Official title: Adjuvant Immunotherapy With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-risk Stage III Melanoma: A Randomized, Double- Blind Phase 3 Trial of the EORTC Melanoma Group
This study will assess whether post-surgery therapy with pembrolizumab improves recurrence-free survival (RFS) as compared to placebo for high-risk participants with melanoma (Stage IIIA [> 1 mm metastasis], IIIB and IIIC). The study will also assess whether pembrolizumab improves RFS versus placebo in the subgroup of participants with programmed cell death-ligand 1 (PD-L1)-positive tumor expression. Participants will be stratified for stage of disease and region and then will be randomly assigned to receive either pembrolizumab or placebo as post-surgery therapy in Part 1. In Part 2, participants who experience a disease recurrence are eligible for pembrolizumab treatment (if treated with placebo in Part 1) or pembrolizumab rechallenge (if treated with pembrolizumab in Part 1).
Read the detailed description
As of Amendment 8, enrollment in Part 2 has closed, and an optional pembrolizumab extension study will not be available to participants after study closure.
- Conditions
- Melanoma
- Being tested
- pembrolizumab, placebo
- Keywords
- Programmed Cell Death-1 (PD-1), Programmed Cell Death 1 (PD1), Programmed Cell Death-Ligand 1 (PD-L1, PDL1), Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabBiological
Also called KEYTRUDA®, MK-3475, SCH 900475
Pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle
placeboDrug
Normal saline solution administered IV on Day 1 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | In Part 1, participants receive pembrolizumab 200 mg intravenously (IV) as post-surgery therapy every 3 weeks (Q3W) for up to 1 year. During Part 2, participants with documented recurrence may receive optional re-treatment with pembrolizumab Q3W for up to 2 years or disease progression. Receives: Biological: pembrolizumab |
| Placebo | Placebo comparator | In Part 1, participants receive placebo IV as post-surgery therapy Q3W. During Part 2, participants with documented recurrence who received placebo in Part 1 may receive optional treatment with pembrolizumab Q3W for up to 2 years or disease progression. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants
RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants in both treatment arms of Part 1.
Measured: 6 months
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among Participants With PD-L1-positive Tumor Expression
RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants with PD-L1-positive tumors in both treatment arms of Part 1.
Measured: 6 months
Secondary outcomes (9)
Distant Metastases-free Survival (DMFS) in All Participants
DMFS will be defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. For participants who remain alive and distant metastasis-free, DMFS will be censored on the date of last visit/contact with disease assessments. The percentage of participants with DMFS will be reported for all participants in both treatment arms.
Measured: Up to approximately 11 years
Distant Metastases-free Survival (DMFS) for Participants With PD-L1-positive Tumor Expression
Description:
DMFS will be defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. For participants who remain alive and distant metastasis-free, DMFS will be censored on the date of last visit/contact with disease assessments. The percentage of participants with DMFS will be reported for all participants with PD-L1-positive tumors in both treatment arms.
Measured: Up to approximately 11 years
Overall Survival (OS) for All Participants
OS will be defined as the time from the date of randomization to the date of death, whatever the cause. The follow-up of participants still alive will be censored at the moment of last visit/contact. OS will be reported for all participants in both treatment arms.
Measured: Up to approximately 11 years
Overall Survival (OS) for Participants With PD-L1-positive Tumor Expression
OS will be defined as the time from the date of randomization to the date of death, whatever the cause. The follow-up of participants still alive will be censored at the moment of last visit/contact. OS will be reported for all participants with PD-L1-positive tumors in both treatment arms.
Measured: Up to approximately 11 years
Number of Participants Who Experienced At Least 1 Adverse Event (AE)
An AE is defined as "any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment". An AE can therefore be any unfavorable and unintended signs (such as rash or enlarged liver), symptoms (such as nausea or chest pain), an abnormal laboratory finding (including results of blood tests, x-rays or scans) or a disease temporarily associated with the use of the protocol treatment, whether or not considered related to the investigational medicinal product. The number of participants who experienced at least 1 AE was reported for all participants in each treatment arm.
Measured: Up to 22 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An AE is defined as "any untoward medical occurrence in a participant which does not necessarily have to have a causal relationship with this treatment". An AE can therefore be any unfavorable and unintended signs (such as rash or enlarged liver), symptoms (such as nausea or chest pain), an abnormal laboratory finding (including results of blood tests, x-rays or scans) or a disease temporarily associated with the use of the protocol treatment, whether or not considered related to the investigational medicinal product. The number of participants who discontinued study treatment due to an AE was reported for all participants in each treatment arm.
Measured: Up to 22 months
Clearance (CL) of Pembrolizumab
Blood samples were to be collected at pre-specified time points and plasma isolated for analysis of pembrolizumab CL, defined as the volume of plasma from which pembrolizumab is eliminated per unit time following IV pembrolizumab administration. Samples were not collected and this analysis was not performed.
Measured: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Volume of Distribution (V) of Pembrolizumab
Blood samples were to be collected at pre-specified time points and plasma isolated for analysis of pembrolizumab V, defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma. Samples were not collected and this analysis was not performed.
Measured: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Number of Participants Positive for Anti-Drug Antibodies (ADA) After Pembrolizumab Treatment
Pre- and post-baseline serum samples from participants treated with pembrolizumab were analyzed for ADA by means of a neutralizing antibody assay which assessed the ability of ADA to block (neutralize) binding of pembrolizumab to Programmed Cell Death-1 (PD-1) protein. Overall immunogenicity was defined as the number of treatment emergent positive participants based on the total number of evaluable participants (treatment emergent positive, non-treatment emergent positive and negative immunogenicity status).
Measured: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2015 (estimated)
- Study start16 Jul 2015
- Primary completion8 Jan 2018
- Study completion1 Nov 2026 (estimated)
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 (9)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,019 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02362594
- Sponsor's protocol ID
- 3475-054
- Other IDs
- 1325-MG, 163277, KEYNOTE-054, MK-3475-054, 2023-509136-25-00, U1111-1309-6016, 2014-004944-37, 2014
- Status last verified
- Feb 2026
- First submitted
- 9 Feb 2015
- Last updated
- 5 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Buhrer E, Kicinski M, Mandala M, Pe M, Long GV, Atkinson V, Blank CU, Haydon A, Dalle S, Khattak A, Carlino MS, Meshcheryakov A, Sandhu S, Puig S, Schadendorf D, Jamal R, Rutkowski P, van den Eertwegh AJM, Coens C, Grebennik D, Krepler C, Robert C, Eggermont AMM. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): long-term, health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2024 Sep;25(9):1202-1212. doi: 10.1016/S1470-2045(24)00338-3. Epub 2024 Aug 12.
PubMed 39146951Eggermont AMM, Kicinski M, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Boers-Sonderen M, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Lorigan P, Grebennik D, Krepler C, Marreaud S, Suciu S, Robert C. Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma. NEJM Evid. 2022 Nov;1(11):EVIDoa2200214. doi: 10.1056/EVIDoa2200214. Epub 2022 Sep 10.
PubMed 38319852Kennedy OJ, Kicinski M, Valpione S, Gandini S, Suciu S, Blank CU, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Robert C, Eggermont AMM, Lorigan P, Mandala M. Prognostic and predictive value of beta-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma. Eur J Cancer. 2022 Apr;165:97-112. doi: 10.1016/j.ejca.2022.01.017. Epub 2022 Feb 24.
PubMed 35220182Bottomley A, Coens C, Mierzynska J, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Puig S, Ascierto PA, Larkin J, Lorigan PC, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C, Eggermont AMM; EORTC Melanoma Group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):655-664. doi: 10.1016/S1470-2045(21)00081-4. Epub 2021 Apr 12.
PubMed 33857414Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C; EORTC Melanoma Group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):643-654. doi: 10.1016/S1470-2045(21)00065-6. Epub 2021 Apr 12.
PubMed 33857412Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C. Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial. J Clin Oncol. 2020 Nov 20;38(33):3925-3936. doi: 10.1200/JCO.20.02110. Epub 2020 Sep 18.
PubMed 32946353Eggermont AMM, Kicinski M, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, Krepler C, Ibrahim N, Marreaud S, van Akkooi A, Robert C, Suciu S. Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2020 Apr 1;6(4):519-527. doi: 10.1001/jamaoncol.2019.5570.
PubMed 31895407van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
PubMed 31395089Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Lichinitser M, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Maio M, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan P, Ibrahim N, Marreaud S, van Akkooi ACJ, Suciu S, Robert C. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018 May 10;378(19):1789-1801. doi: 10.1056/NEJMoa1802357. Epub 2018 Apr 15.
PubMed 29658430
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Immunotherapy With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-risk Stage III Melanoma: A Randomized, Double- Blind Phase 3 Trial of the EORTC Melanoma Group
- ClinicalTrials.gov ID
- NCT02362594
- Acronym / sponsor ID
- 3475-054
- Conditions
- Melanoma
- Keywords
- Programmed Cell Death-1 (PD-1), Programmed Cell Death 1 (PD1), Programmed Cell Death-Ligand 1 (PD-L1, PDL1), Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,019 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- European Organisation for Research and Treatment of Cancer - EORTC
- Study start
- 16 Jul 2015 (actual)
- Primary completion
- 8 Jan 2018 (actual)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 13 Feb 2015 (estimated)
- Results
- Posted 4 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess whether post-surgery therapy with pembrolizumab improves recurrence-free survival (RFS) as compared to placebo for high-risk participants with melanoma (Stage IIIA [> 1 mm metastasis], IIIB and IIIC). The study will also assess whether pembrolizumab improves RFS versus placebo in the subgroup of participants with programmed cell death-ligand 1 (PD-L1)-positive tumor expression. Participants will be stratified for stage of disease and region and then will be randomly assigned to receive either pembrolizumab or placebo as post-surgery therapy in Part 1. In Part 2, participants who experience a disease recurrence are eligible for pembrolizumab treatment (if treated with placebo in Part 1) or pembrolizumab rechallenge (if treated with pembrolizumab in Part 1).
Detailed description
As of Amendment 8, enrollment in Part 2 has closed, and an optional pembrolizumab extension study will not be available to participants after study closure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Biological: pembrolizumabIn Part 1, participants receive pembrolizumab 200 mg intravenously (IV) as post-surgery therapy every 3 weeks (Q3W) for up to 1 year. During Part 2, participants with documented recurrence may receive optional re-treatment with pembrolizumab Q3W for up to 2 years or disease progression. |
| Placebo | Placebo comparator | Drug: placeboIn Part 1, participants receive placebo IV as post-surgery therapy Q3W. During Part 2, participants with documented recurrence who received placebo in Part 1 may receive optional treatment with pembrolizumab Q3W for up to 2 years or disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Completely resected Stage III melanoma
- Tumor tissue available for evaluation of PD-L1 expression
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
- No prior therapy for melanoma except surgery for primary melanoma lesions (or previously treated with interferon for thick primary melanomas without evidence of lymph node involvement are eligible)
Key exclusion criteria (15 listed)
- Mucosal or ocular melanoma
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- History of or current interstitial lung disease
- History of hematologic or primary solid tumor malignancy, unless no evidence of that disease for 5 years
- Active autoimmune disease that has required systemic treatment in past 2 years
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 |
|---|---|---|
| pembrolizumabAlso: KEYTRUDA®, MK-3475, SCH 900475Pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle | Biological | Pembrolizumab |
| placeboNormal saline solution administered IV on Day 1 of each 21-day cycle | Drug | Placebo |
Primary outcome
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants
Time frame: 6 months
RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants in both treatment arms of Part 1.
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among Participants With PD-L1-positive Tumor Expression
Time frame: 6 months
RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants with PD-L1-positive tumors in both treatment arms of Part 1.
9 secondary outcomes
Distant Metastases-free Survival (DMFS) in All Participants
Time frame: Up to approximately 11 years
Distant Metastases-free Survival (DMFS) for Participants With PD-L1-positive Tumor Expression
Time frame: Up to approximately 11 years
Overall Survival (OS) for All Participants
Time frame: Up to approximately 11 years
Overall Survival (OS) for Participants With PD-L1-positive Tumor Expression
Time frame: Up to approximately 11 years
Number of Participants Who Experienced At Least 1 Adverse Event (AE)
Time frame: Up to 22 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time frame: Up to 22 months
Clearance (CL) of Pembrolizumab
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Volume of Distribution (V) of Pembrolizumab
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Number of Participants Positive for Anti-Drug Antibodies (ADA) After Pembrolizumab Treatment
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39146951Buhrer E, Kicinski M, Mandala M, Pe M, Long GV, Atkinson V, Blank CU, Haydon A, Dalle S, Khattak A, Carlino MS, Meshcheryakov A, Sandhu S, Puig S, Schadendorf D, Jamal R, Rutkowski P, van den Eertwegh AJM, Coens C, Grebennik D, Krepler C, Robert C, Eggermont AMM. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): long-term, health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2024 Sep;25(9):1202-1212. doi: 10.1016/S1470-2045(24)00338-3. Epub 2024 Aug 12.
- Derived from this study: PubMed 38319852Eggermont AMM, Kicinski M, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Boers-Sonderen M, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Lorigan P, Grebennik D, Krepler C, Marreaud S, Suciu S, Robert C. Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma. NEJM Evid. 2022 Nov;1(11):EVIDoa2200214. doi: 10.1056/EVIDoa2200214. Epub 2022 Sep 10.
- Derived from this study: PubMed 35220182Kennedy OJ, Kicinski M, Valpione S, Gandini S, Suciu S, Blank CU, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Robert C, Eggermont AMM, Lorigan P, Mandala M. Prognostic and predictive value of beta-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma. Eur J Cancer. 2022 Apr;165:97-112. doi: 10.1016/j.ejca.2022.01.017. Epub 2022 Feb 24.
- Derived from this study: PubMed 33857414Bottomley A, Coens C, Mierzynska J, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Puig S, Ascierto PA, Larkin J, Lorigan PC, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C, Eggermont AMM; EORTC Melanoma Group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):655-664. doi: 10.1016/S1470-2045(21)00081-4. Epub 2021 Apr 12.
- Derived from this study: PubMed 33857412Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C; EORTC Melanoma Group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):643-654. doi: 10.1016/S1470-2045(21)00065-6. Epub 2021 Apr 12.
- Derived from this study: PubMed 32946353Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C. Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial. J Clin Oncol. 2020 Nov 20;38(33):3925-3936. doi: 10.1200/JCO.20.02110. Epub 2020 Sep 18.
- Derived from this study: PubMed 31895407Eggermont AMM, Kicinski M, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, Krepler C, Ibrahim N, Marreaud S, van Akkooi A, Robert C, Suciu S. Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2020 Apr 1;6(4):519-527. doi: 10.1001/jamaoncol.2019.5570.
- Derived from this study: PubMed 31395089van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
- Derived from this study: PubMed 29658430Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Lichinitser M, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Maio M, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan P, Ibrahim N, Marreaud S, van Akkooi ACJ, Suciu S, Robert C. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018 May 10;378(19):1789-1801. doi: 10.1056/NEJMoa1802357. Epub 2018 Apr 15.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Plain Language SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pembrolizumab in people with Melanoma, run by Merck Sharp & Dohme LLC.
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 7 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 4 Jan 2019). 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?
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT02362594, which also lists 9 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 5 Mar 2026.