A Phase 3 interventional study of pembrolizumab and placebo in Melanoma, sponsored by Merck Sharp & Dohme LLC. Active, not recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-05.
Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment
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).
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.
3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.
This study's enrollment of 1,019 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.
Browse Melanoma studies →Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.
Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion criteria:
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.
Biological: pembrolizumab
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.
Drug: placebo
Pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle
Also known as: KEYTRUDA®, MK-3475, SCH 900475
Normal saline solution administered IV on Day 1 of each 21-day cycle
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.
Time frame: 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.
Time frame: 6 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
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
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).
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.
| Milestone | Pembrolizumab | Placebo |
|---|---|---|
| Started | 514 | 505 |
| Treated | 509 | 502 |
| Continuing part 1 adjuvant therapy | 41 | 21 |
| Completed | 264 | 280 |
| Not completed | 250 | 225 |
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.
| Percentage of Participants | Pembrolizumab | Placebo |
|---|---|---|
| Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants | 82.2 (78.6 to 85.3) | 73.3 (69.2 to 77.0) |
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.
| Percentage of Participants | Pembrolizumab | Placebo |
|---|---|---|
| Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among Participants With PD-L1-positive Tumor Expression | 83.8 (80.0 to 87.0) | 75.4 (71.0 to 79.2) |
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
| Participants | Pembrolizumab | Placebo |
|---|---|---|
| Number of Participants Who Experienced At Least 1 Adverse Event (AE) | 475 | 453 |
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.
| Participants | Pembrolizumab | Placebo |
|---|---|---|
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 70 | 18 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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).
| Participants | Pembrolizumab | Placebo |
|---|---|---|
| Negative | 473 | — |
| Non-Treatment emergent positive | 5 | — |
| Treatment emergent positive | 17 | — |
Collected over Up to 29 months (through database cut-off date of 02-Oct-2017). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pembrolizumab | 25/514 (4.9%) | 128/509 (25.1%) | 443/509 (87%) |
| Placebo | 35/505 (6.9%) | 82/502 (16.3%) | 409/502 (81.5%) |
| Event | Pembrolizumab | Placebo |
|---|---|---|
| Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 17/509 | 25/502 |
| ColitisGastrointestinal disorders | 8/509 | 0/502 |
| CellulitisInfections and infestations | 3/509 | 7/502 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 7/509 | 0/502 |
| Malignant melanoma in situNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/509 | 6/502 |
| Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 6/509 | 3/502 |
| DiarrhoeaGastrointestinal disorders | 5/509 | 2/502 |
| ErysipelasInfections and infestations | 2/509 | 4/502 |
| PyrexiaGeneral disorders | 4/509 | 0/502 |
| Bowen's diseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 4/509 | 1/502 |
| Event | Pembrolizumab | Placebo |
|---|---|---|
| FatigueGeneral disorders | 168/509 | 168/502 |
| DiarrhoeaGastrointestinal disorders | 140/509 | 129/502 |
| PruritusSkin and subcutaneous tissue disorders | 99/509 | 58/502 |
| HeadacheNervous system disorders | 95/509 | 93/502 |
| NauseaGastrointestinal disorders | 88/509 | 73/502 |
| Weight increasedInvestigations | 63/509 | 82/502 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 79/509 | 72/502 |
| HypertensionVascular disorders | 74/509 | 77/502 |
| HypothyroidismEndocrine disorders | 75/509 | 14/502 |
| CoughRespiratory, thoracic and mediastinal disorders | 70/509 | 55/502 |
| Age, Continuous(Years) | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| Mean | 53.9 ± 13.6 | 53.7 ± 14.2 | 53.8 ± 13.9 |
| Sex: Female, Male(Participants) | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| Female | 190 | 201 | 391 |
| Male | 324 | 304 | 628 |
| Race and Ethnicity Not Collected(Participants) | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Programmed Death-Ligand 1 (PD-L1) Tumor Status(Participants) | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| PD-L1 Positive | 428 | 425 | 853 |
| PD-L1 Negative | 59 | 57 | 116 |
| Undetermined | 27 | 23 | 50 |
| Melanoma Stage(Participants) | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| Stage IIIA (> 1 mm) | 80 | 80 | 160 |
| Stage IIIB | 237 | 230 | 467 |
| Stage IIIC (1-3 LN+) | 95 | 93 | 188 |
| Stage IIIC (≥4 LN+) | 102 | 102 | 204 |
| Region of Enrollment(Participants) | Pembrolizumab | Placebo | Total |
|---|---|---|---|
| North America | 38 | 37 | 75 |
| Europe | 341 | 336 | 677 |
| Australia/New Zealand | 111 | 112 | 223 |
| Other | 24 | 20 | 44 |
No study locations are listed for this record.
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This study is active, not recruiting, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
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Merck Sharp & Dohme LLC