Non-small Cell Lung CancerPhase 3PEARLSNCT02504372
Study of Pembrolizumab (MK-3475) vs Placebo for Participants With Non-small Cell Lung Cancer After Resection With or Without Standard Adjuvant Therapy (MK-3475-091/KEYNOTE-091)
A Phase 3 study testing Pembrolizumab in people with Non-small Cell Lung Cancer, run by Merck Sharp & Dohme LLC.
Trial summary
In this study, participants with Stage IB/II-IIIA non-small cell lung cancer (NSCLC) who have undergone surgical resection (lobectomy or pneumonectomy) with or without adjuvant chemotherapy will be treated with pembrolizumab or placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- 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
- 1,177 participants
- Where
- No sites listed yet
- Study dates
- 6 Nov 2015to 21 Jan 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
- Pathological diagnosis of NSCLC confirmed at surgery, any histology. Participants with two synchronous primary non-small cell lung cancers are excluded from the study
- Union for International Cancer Control (UICC) v7 Stage IB with T ≥ 4 cm, II-IIIA NSCLC after complete surgical resection with resection margins proved microscopically free of disease (R0). Carcinoma in situ can be present at the bronchial margin
- Available tumor sample obtained at surgical resection for programmed cell death ligand-1 (PD-L1) Immunohistochemistry (IHC) expression assessment
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Adequate organ function performed within 10 days of treatment initiation
- Female participants of childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first infusion of study medication). If the urine test cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the participant to be eligible
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- Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity starting with the first infusion of study treatment through 120 days after the last infusion of study treatment
- Female participants who are breast feeding must discontinue nursing prior to the first infusion of study medication and until 120 days after the last infusion study treatment
- Male participants must agree to use an adequate method of contraception starting with the first infusion of study treatment through 120 days after the last infusion of study treatment
- Absence of severe comorbidities that in the opinion of the Investigator might hamper the participation to the study and/or the treatment administration
- No prior or planned neo-adjuvant or adjuvant radiotherapy and/or neo-adjuvant chemotherapy for the current malignancy is allowed
Who cannot join
- Evidence of disease at clinical examination and/or baseline radiological assessment as documented by contrast enhanced chest/upper abdomen CT scan, brain CT/MRI and clinical examination
- More than 4 cycles of adjuvant therapy
- Prior treatment with anti-programmed cell death (anti-PD)-1, anti-PD ligand-1/2, anti-CD137, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) modulators or any other immune-modulating agents
- Live vaccine within 30 days prior to the first infusion of study treatment
- Current participation or treatment with an investigational agent or use of an investigational device within 4 weeks of the first infusion of study treatment
- History of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive). No known active Hepatitis B or C
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- Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 3 days prior to the first infusion of study treatment
- History of interstitial lung disease or (non-infectious) pneumonitis that required oral or IV steroids (other than COPD exacerbation) or current pneumonitis
- Active autoimmune disease that has required systemic treatment in past 2 years
- History of a hematologic or primary solid tumor malignancy, unless in remission for at least 5 years with the exception of pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix
- Previous allogeneic tissue/solid organ transplant
- Active infection requiring therapy
- Surgery- or chemotherapy-related toxicity (non-hematological) not resolved to Grade 1 with the exception of alopecia, fatigue, neuropathy and lack of appetite /nausea
- 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 infusion of study treatment
- Participant will not be eligible if the 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, unless prospective site Review Board approval is given allowing exception to this criterion for a specific participant
About this study
Official title: A Randomized, Phase 3 Trial With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) Versus Placebo for Patients With Early Stage NSCLC After Resection and Completion of Standard Adjuvant Therapy (PEARLS)
In this study, participants with Stage IB/II-IIIA non-small cell lung cancer (NSCLC) who have undergone surgical resection (lobectomy or pneumonectomy) with or without adjuvant chemotherapy will be treated with pembrolizumab or placebo. The primary study hypothesis is that pembrolizumab will provide improved disease-free survival (DFS) versus placebo.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Pembrolizumab, Placebo
- Keywords
- Non-small cell lung cancer (NSCLC), Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand (PDL)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion
PlaceboOther
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Participants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks, for one year (expected maximum 18 doses). Receives: Biological: Pembrolizumab |
| Placebo | Placebo comparator | Participants receive placebo, IV, every 3 weeks, for one year (expected maximum 18 doses). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Free Survival (DFS)
DFS was defined as the time from randomization to either the date of disease recurrence or death (whatever the cause) as assessed by the investigator. Recurrence of disease was defined as local regional recurrence, a distant (metastatic) recurrence, or a second primary cancer. Occurrence of a second extra-pulmonary malignancy was considered to be an event.
Measured: Up to approximately 84 months
DFS in Programmed Death Ligand-1 (PDL-1) Strong Positive Participants With Tumor Proportion Score (TPS) ≥50%
DFS in PDL-1 strong positive participants with TPS ≥50% was defined as the time from randomization to either the date of disease recurrence or death (whatever the cause) as assessed by the investigator. Recurrence of disease was defined as local regional recurrence, a distant (metastatic) recurrence, or a second primary cancer. Occurrence of a second extra-pulmonary malignancy was considered to be an event.
Measured: Up to approximately 84 months
Secondary outcomes (7)
DFS in PDL-1 Strong Positive Participants With TPS ≥1%
DFS in PDL-1 strong positive participants with TPS ≥1% was defined as the time from randomization to either the date of disease recurrence or death (whatever the cause) as assessed by the investigator. Recurrence of disease was defined as local regional recurrence, a distant (metastatic) recurrence, or a second primary cancer. Occurrence of a second extra-pulmonary malignancy was considered to be an event.
Measured: Up to approximately 84 months
Overall Survival (OS)
OS was defined as the time from randomization to the date of death.
Measured: Up to approximately 132 months
OS in PDL-1 Strong Positive Participants With TPS ≥50%
OS in PDL-1 Strong Positive Participants with TPS ≥50% was defined as the time from randomization to the date of death.
Measured: Up to approximately 132 months
OS in PDL-1 Strong Positive Participants With TPS ≥1%
OS in PDL-1 Strong Positive Participants with TPS ≥1% was defined as the time from randomization to the date of death.
Measured: Up to approximately 132 months
Lung Cancer Specific Survival (LCSS)
LCSS was defined as the time from randomization to the date of death (due to lung cancer specifically).
Measured: Up to approximately 132 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. The number of participants who experienced an AE were reported.
Measured: Up to approximately 22 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. The number of participants who discontinued study treatment due to an AE were reported.
Measured: Up to approximately 19 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start6 Nov 2015
- Primary completion24 Jan 2023
- Study completion21 Jan 2026
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 (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,177 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ETOP, European Organisation for Research and Treatment of Cancer - EORTC
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504372
- Sponsor's protocol ID
- 3475-091
- Other IDs
- EORTC-1416-LCG, 163457, MK-3475-091, KEYNOTE-091, 2023-509137-39-00, U1111-1309-6051, 2015-000575-27, 2015
- Acronym
- PEARLS
- Status last verified
- Feb 2026
- First submitted
- 20 Jul 2015
- Last updated
- 17 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, Esteban E, Isla D, Martinez-Marti A, Faehling M, Tsuboi M, Lee JS, Nakagawa K, Yang J, Samkari A, Keller SM, Mauer M, Jha N, Stahel R, Besse B, Peters S; EORTC-1416-LCG/ETOP 8-15 - PEARLS/KEYNOTE-091 Investigators. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1274-1286. doi: 10.1016/S1470-2045(22)00518-6. Epub 2022 Sep 12.
PubMed 36108662
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Phase 3 Trial With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) Versus Placebo for Patients With Early Stage NSCLC After Resection and Completion of Standard Adjuvant Therapy (PEARLS)
- ClinicalTrials.gov ID
- NCT02504372
- Acronym / sponsor ID
- PEARLS / 3475-091
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Non-small cell lung cancer (NSCLC), Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand (PDL)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,177 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- ETOP, European Organisation for Research and Treatment of Cancer - EORTC
- Study start
- 6 Nov 2015 (actual)
- Primary completion
- 24 Jan 2023 (actual)
- Study completion
- 21 Jan 2026 (actual)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Posted 15 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, participants with Stage IB/II-IIIA non-small cell lung cancer (NSCLC) who have undergone surgical resection (lobectomy or pneumonectomy) with or without adjuvant chemotherapy will be treated with pembrolizumab or placebo. The primary study hypothesis is that pembrolizumab will provide improved disease-free survival (DFS) versus placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Biological: PembrolizumabParticipants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks, for one year (expected maximum 18 doses). |
| Placebo | Placebo comparator | Other: PlaceboParticipants receive placebo, IV, every 3 weeks, for one year (expected maximum 18 doses). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pathological diagnosis of NSCLC confirmed at surgery, any histology. Participants with two synchronous primary non-small cell lung cancers are excluded from the study
- Union for International Cancer Control (UICC) v7 Stage IB with T ≥ 4 cm, II-IIIA NSCLC after complete surgical resection with resection margins proved microscopically free of disease (R0). Carcinoma in situ can be present at the bronchial margin
- Available tumor sample obtained at surgical resection for programmed cell death ligand-1 (PD-L1) Immunohistochemistry (IHC) expression assessment
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Adequate organ function performed within 10 days of treatment initiation
Key exclusion criteria (15 listed)
- Evidence of disease at clinical examination and/or baseline radiological assessment as documented by contrast enhanced chest/upper abdomen CT scan, brain CT/MRI and clinical examination
- More than 4 cycles of adjuvant therapy
- Prior treatment with anti-programmed cell death (anti-PD)-1, anti-PD ligand-1/2, anti-CD137, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) modulators or any other immune-modulating agents
- Live vaccine within 30 days prior to the first infusion of study treatment
- Current participation or treatment with an investigational agent or use of an investigational device within 4 weeks of the first infusion of study treatment
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: MK-3475, KEYTRUDA®IV infusion | Biological | Pembrolizumab |
| PlaceboIV infusion | Other | Placebo |
Primary outcome
Disease-Free Survival (DFS)
Time frame: Up to approximately 84 months
DFS was defined as the time from randomization to either the date of disease recurrence or death (whatever the cause) as assessed by the investigator. Recurrence of disease was defined as local regional recurrence, a distant (metastatic) recurrence, or a second primary cancer. Occurrence of a second extra-pulmonary malignancy was considered to be an event.
DFS in Programmed Death Ligand-1 (PDL-1) Strong Positive Participants With Tumor Proportion Score (TPS) ≥50%
Time frame: Up to approximately 84 months
DFS in PDL-1 strong positive participants with TPS ≥50% was defined as the time from randomization to either the date of disease recurrence or death (whatever the cause) as assessed by the investigator. Recurrence of disease was defined as local regional recurrence, a distant (metastatic) recurrence, or a second primary cancer. Occurrence of a second extra-pulmonary malignancy was considered to be an event.
7 secondary outcomes
DFS in PDL-1 Strong Positive Participants With TPS ≥1%
Time frame: Up to approximately 84 months
Overall Survival (OS)
Time frame: Up to approximately 132 months
OS in PDL-1 Strong Positive Participants With TPS ≥50%
Time frame: Up to approximately 132 months
OS in PDL-1 Strong Positive Participants With TPS ≥1%
Time frame: Up to approximately 132 months
Lung Cancer Specific Survival (LCSS)
Time frame: Up to approximately 132 months
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 22 months
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximately 19 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36108662O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, Esteban E, Isla D, Martinez-Marti A, Faehling M, Tsuboi M, Lee JS, Nakagawa K, Yang J, Samkari A, Keller SM, Mauer M, Jha N, Stahel R, Besse B, Peters S; EORTC-1416-LCG/ETOP 8-15 - PEARLS/KEYNOTE-091 Investigators. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1274-1286. doi: 10.1016/S1470-2045(22)00518-6. Epub 2022 Sep 12.
- Merck Clinical Trials InformationLink 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 Non-small Cell Lung Cancer, 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 11 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: finished, as of the sponsor's last update on 17 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 15 Feb 2024). 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?
Disease-Free Survival (DFS) (time frame: Up to approximately 84 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 NCT02504372, which also lists 1 linked publication.
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 17 Mar 2026.