NCT02504372 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-03-17

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease-Free Survival (DFS)

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outcome · POSTED

DFS in Programmed Death Ligand-1 (PDL-1) Strong Positive Participants With Tumor Proportion Score (TPS) ≥50%

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outcome · POSTED

DFS in PDL-1 Strong Positive Participants With TPS ≥1%

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · NOT POSTED

OS in PDL-1 Strong Positive Participants With TPS ≥50%

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outcome · NOT POSTED

OS in PDL-1 Strong Positive Participants With TPS ≥1%

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outcome · NOT POSTED

Lung Cancer Specific Survival (LCSS)

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outcome · POSTED

Number of Participants Who Experienced an Adverse Event (AE)

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outcome · POSTED

Number of Participants Who Discontinued Study Treatment Due to an AE

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outcome · POSTED

DFS at 68 Months

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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 * 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks, for one year (expected maximum 18 doses).
intervention Names
Biological: Pembrolizumab
label
Pembrolizumab
type
EXPERIMENTAL
description
Participants receive placebo, IV, every 3 weeks, for one year (expected maximum 18 doses).
intervention Names
Other: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Pembrolizumab
description
IV infusion
name
Pembrolizumab
other Names
MK-3475
KEYTRUDA®
type
BIOLOGICAL
arm Group Labels
Placebo
description
IV infusion
name
Placebo
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 1177
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
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.
measure
DFS at 68 Months
time Frame
Up to approximately 68 months

primary Outcomes

description
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.
measure
Disease-Free Survival (DFS)
time Frame
Up to approximately 84 months
description
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.
measure
DFS in Programmed Death Ligand-1 (PDL-1) Strong Positive Participants With Tumor Proportion Score (TPS) ≥50%
time Frame
Up to approximately 84 months

secondary Outcomes

description
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.
measure
DFS in PDL-1 Strong Positive Participants With TPS ≥1%
time Frame
Up to approximately 84 months
description
OS was defined as the time from randomization to the date of death.
measure
Overall Survival (OS)
time Frame
Up to approximately 132 months
description
OS in PDL-1 Strong Positive Participants with TPS ≥50% was defined as the time from randomization to the date of death.
measure
OS in PDL-1 Strong Positive Participants With TPS ≥50%
time Frame
Up to approximately 132 months
description
OS in PDL-1 Strong Positive Participants with TPS ≥1% was defined as the time from randomization to the date of death.
measure
OS in PDL-1 Strong Positive Participants With TPS ≥1%
time Frame
Up to approximately 132 months
description
LCSS was defined as the time from randomization to the date of death (due to lung cancer specifically).
measure
Lung Cancer Specific Survival (LCSS)
time Frame
Up to approximately 132 months
description
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.
measure
Number of Participants Who Experienced an Adverse Event (AE)
time Frame
Up to approximately 22 months
description
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.
measure
Number of Participants Who Discontinued Study Treatment Due to an AE
time Frame
Up to approximately 19 months

Full study description

brief 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. The primary study hypothesis is that pembrolizumab will provide improved disease-free survival (DFS) versus placebo.

Source references

references

citation
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.
pmid
36108662
type
DERIVED