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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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

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.

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 groups in NCT02504372
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks, for one year (expected maximum 18 doses).
Receives: Biological: Pembrolizumab
PlaceboPlacebo comparatorParticipants 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.

  1. 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

  2. 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)

  1. 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

  2. Overall Survival (OS)

    OS was defined as the time from randomization to the date of death.

    Measured: Up to approximately 132 months

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  1. First posted21 Jul 2015 (estimated)
  2. Study start6 Nov 2015
  3. Primary completion24 Jan 2023
  4. Study completion21 Jan 2026

Resources

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)
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
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

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