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)

NCT ID: NCT02504372

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-06
• Study Completion Date: 2026-01-21

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pembrolizumab

Participants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks, for one year (expected maximum 18 doses).

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Placebo

Participants receive placebo, IV, every 3 weeks, for one year (expected maximum 18 doses).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

IV infusion

Interventions

Pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

Placebo

IV infusion

Intervention Type: OTHER

Other Intervention Names

MK-3475; KEYTRUDA®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ETOP

UNKNOWN

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 36108662 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

EORTC-1416-LCG

Identifier Type: OTHER

Identifier Source: secondary_id

163457

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-091

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-091

Identifier Type: OTHER

Identifier Source: secondary_id

2023-509137-39-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1309-6051

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-000575-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-091

Identifier Type: -

Identifier Source: org_study_id