- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02504372
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)
February 13, 2024 updated by: Merck Sharp & Dohme LLC
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
1177
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg, intravenously (IV), every 3 weeks, for one year (expected maximum 18 doses).
|
IV infusion
Other Names:
|
Placebo Comparator: Placebo
Participants receive placebo, IV, every 3 weeks, for one year (expected maximum 18 doses).
|
IV infusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to approximately 84 months
|
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.
|
Up to approximately 84 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DFS in PDL-1 Strong Positive Participants With TPS ≥1%
Time Frame: Up to approximately 84 months
|
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.
|
Up to approximately 84 months
|
Overall Survival (OS)
Time Frame: Up to approximately 132 months
|
OS was defined as the time from randomization to the date of death.
|
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 ≥50% was defined as the time from randomization to the date of death.
|
Up to approximately 132 months
|
OS in PDL-1 Strong Positive Participants With TPS ≥1%
Time Frame: Up to approximately 132 months
|
OS in PDL-1 Strong Positive Participants with TPS ≥1% was defined as the time from randomization to the date of death.
|
Up to approximately 132 months
|
Lung Cancer Specific Survival (LCSS)
Time Frame: Up to approximately 132 months
|
LCSS was defined as the time from randomization to the date of death (due to lung cancer specifically).
|
Up to approximately 132 months
|
Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to approximately 22 months
|
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.
|
Up to approximately 22 months
|
Number of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: Up to approximately 19 months
|
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.
|
Up to approximately 19 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DFS at 68 Months
Time Frame: Up to approximately 68 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.
|
Up to approximately 68 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 6, 2015
Primary Completion (Actual)
January 24, 2023
Study Completion (Estimated)
February 2, 2027
Study Registration Dates
First Submitted
July 20, 2015
First Submitted That Met QC Criteria
July 20, 2015
First Posted (Estimated)
July 21, 2015
Study Record Updates
Last Update Posted (Actual)
February 15, 2024
Last Update Submitted That Met QC Criteria
February 13, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- 3475-091
- 2015-000575-27 (EudraCT Number)
- EORTC-1416-LCG (Other Identifier: EORTC)
- 163457 (Registry Identifier: JAPIC-CTI)
- MK-3475-091 (Other Identifier: Merck)
- KEYNOTE-091 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Non-small Cell Lung Cancer
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
Alexander ChiNot yet recruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Carcinoma | Non-small Cell Lung Cancer Stage IIChina
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
National Cancer Institute (NCI)Not yet recruitingStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerCanada
-
Karen KellyBristol-Myers Squibb; National Cancer Institute (NCI); TransgeneCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung CancerUnited States
-
Memorial Sloan Kettering Cancer CenterAstraZenecaRecruitingNSCLC | Lung Cancer | Non-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | PD-L1 Gene Mutation | Non-small Cell Lung Cancer Stage IIIA | Non-small Cell Lung Cancer Stage IIUnited States
-
Virginia Commonwealth UniversityNational Cancer Institute (NCI)WithdrawnStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
Clinical Trials on Pembrolizumab
-
University Medical Center GroningenCompleted
-
Incyte CorporationMerck Sharp & Dohme LLCCompletedMelanomaUnited States, France, Italy, United Kingdom, Spain, Belgium, Israel, Mexico, Japan, Canada, Netherlands, Sweden, Korea, Republic of, Australia, Russian Federation, Chile, Germany, Poland, Ireland, New Zealand, Denmark, Switzerland, South Africa
-
Merck Sharp & Dohme LLCCompletedMelanomaAustralia, South Africa, Spain, Sweden
-
Acerta Pharma BVMerck Sharp & Dohme LLCCompletedMetastatic Urothelial CarcinomaUnited States
-
HUYABIO International, LLC.Active, not recruitingNon Small Cell Lung CancerUnited States
-
Sichuan UniversityGeneplus-Beijing Co. Ltd.RecruitingNon-small Cell Lung CancerChina
-
Chinese University of Hong KongCompletedAcral Lentiginous MelanomaHong Kong
-
Prof. Dr. Matthias PreusserUnknownPrimary Central Nervous System LymphomaAustria
-
Samsung Medical CenterRecruitingMetastatic Non-Small Cell Lung CarcinomaKorea, Republic of