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)

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2024
• Main ID: NCT02504372
• Date of registration: 20/07/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: 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) PEARLS
• Scientific 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)
• Date of first enrolment: November 6, 2015
• Target sample size: 1177
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02504372
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Netherlands, Peru, Poland, Portugal, Russian Federation, Slovenia, Spain, Switzerland, Turkey, United Kingdom

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-small Cell Lung Cancer

Intervention(s)

Biological: Pembrolizumab

Other: Placebo

Primary Outcome(s)

DFS in Programmed Death Ligand-1 (PDL-1) Strong Positive Participants With Tumor Proportion Score (TPS) =50% [Time Frame: Up to approximately 84 months]

Disease-Free Survival (DFS) [Time Frame: Up to approximately 84 months]

Secondary Outcome(s)

Number of Participants Who Discontinued Study Treatment Due to an AE [Time Frame: Up to approximately 19 months]

Overall Survival (OS) [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]

DFS in PDL-1 Strong Positive Participants With TPS =1% [Time Frame: Up to approximately 84 months]

Number of Participants Who Experienced an Adverse Event (AE) [Time Frame: Up to approximately 22 months]

OS in PDL-1 Strong Positive Participants With TPS =50% [Time Frame: Up to approximately 132 months]

Secondary ID(s)

EORTC-1416-LCG

163457

KEYNOTE-091

3475-091

2015-000575-27

MK-3475-091

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

European Organisation for Research and Treatment of Cancer - EORTC

ETOP

Results

• Results available: Yes
• Date Posted: 15/02/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02504372