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Study of Pembrolizumab (MK-3475) in Participants With Advanced Non-small Cell Lung Cancer (MK-3475-025/KEYNOTE-025)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02007070
Recruitment Status : Completed
First Posted : December 10, 2013
Results First Posted : December 5, 2016
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE December 5, 2013
First Posted Date  ICMJE December 10, 2013
Results First Submitted Date  ICMJE May 31, 2016
Results First Posted Date  ICMJE December 5, 2016
Last Update Posted Date August 31, 2018
Actual Study Start Date  ICMJE February 28, 2014
Actual Primary Completion Date July 9, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
  • Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    On-study imaging was to be performed every 9 weeks after the first dose of study drug, or more frequently if clinically indicated. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The percentage of strongly PD-L1 positive participants who experienced a CR or PR is presented.
  • Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 27 months (Up to 90 days after last dose of study drug) ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), 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. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. After discontinuation of study drug, each participant was monitored for a minimum of 30 days for AE monitoring (serious AEs were monitored for up to 90 days after last dose of study drug). The number of participants who experienced an AE is presented.
  • Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to 2 years ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), 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. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. The number of participants who discontinued study drug due to an AE is presented.
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2013)
  • Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to 2 years ]
  • Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 2 years ]
  • Number of participants discontinuing study treatment due to AEs [ Time Frame: Up to 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
  • Progression Free Survival (PFS) by RECIST 1.1 in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central radiologists' review or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm in the sum of lesions, OR the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. The median PFS for all strongly PD-L1 positive participants is presented.
  • Duration of Response (DOR) by RECIST 1.1 in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed using the Kaplan-Meier method and is reported in days. The median DOR for all strongly PD-L1 positive participants with a confirmed response is presented.
  • Overall Survival (OS) in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    OS was defined as the time from the first day of study treatment to death due to any cause. OS is reported for all strongly PD-L1 positive participants in months
  • ORR Per Immune-Related Response Criteria (irRC) in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    ORR per irRC was defined as the percentage of participants in the analysis population who had a Complete Response (irCR: Complete disappearance of all tumor lesions [whether measureable or not, and no new lesions; irCR must be confirmed by repeated, consecutive assessments made no less than 4 weeks from the date first documented]) or Partial Response (irPR: Decrease in sum of the products of the two largest perpendicular diameters [SPD] of 50% or greater by a consecutive assessment at least 4 weeks after first documentation). The percentage of strongly PD-L1 positive participants who experienced an irCR or irPR is presented.
  • PFS Per irRC in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRC or death due to any cause, whichever occurred first. Using irRC, progressive disease was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. Median PFS was analyzed using the Kaplan-Meier method and is presented in months for all strongly PD-L1 positive participants.
  • DOR Per irRC in Strongly PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    DOR was measured from the time measurement criteria were first met for irCR/irPR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). PD was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method, is reported in days and is presented for all strongly PD-L1 positive participants who experienced an irCR or irPR.
  • ORR Per RECIST 1.1 in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    On-study imaging was to be performed every 9 weeks after the first dose of study drug, or more frequently if clinically indicated. ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The percentage of PD-L1 positive participants who experienced a CR or PR is presented.
  • PFS by RECIST 1.1 in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central radiologists' review or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm in the sum of lesions, OR the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. The median PFS for all PD-L1 positive participants is presented.
  • DOR by RECIST 1.1 in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed using the Kaplan-Meier method and is reported in days. The median DOR for all PD-L1 positive participants with a confirmed response is presented.
  • OS in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    OS was defined as the time from the first day of study treatment to death due to any cause. OS is reported for all PD-L1 positive participants in months.
  • ORR Per irRC in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    ORR per irRC was defined as the percentage of participants in the analysis population who had a irCR (Complete disappearance of all tumor lesions [whether measureable or not, and no new lesions; irCR must be confirmed by repeated, consecutive assessments made no less than 4 weeks from the date first documented]) or irPR (Decrease in sum of the products of the two largest perpendicular diameters [SPD] of 50% or greater by a consecutive assessment at least 4 weeks after first documentation). The percentage of PD-L1 positive participants who experienced an irCR or irPR is presented.
  • PFS Per irRC in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRC or death due to any cause, whichever occurred first. Using irRC, progressive disease was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. Median PFS was analyzed using the Kaplan-Meier method and is presented in months for all PD-L1 positive participants.
  • DOR Per irRC in PD-L1 Positive Participants [ Time Frame: Up to 2 years ]
    DOR was measured from the time measurement criteria were first met for irCR/irPR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). PD was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method, is reported in days and is presented for all PD-L1 positive participants who experienced an irCR or irPR.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2013)
  • Progression Free Survival (PFS) by RECIST 1.1 [ Time Frame: Up to 2 years ]
  • Duration of Response (DOR) by RECIST 1.1 [ Time Frame: Up to 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) in Participants With Advanced Non-small Cell Lung Cancer (MK-3475-025/KEYNOTE-025)
Official Title  ICMJE An Open-label, Non-randomized, Multi-center Phase Ib Study of MK-3475 in Subjects With PD-L1 Positive Advanced Non-small Cell Lung Cancer
Brief Summary This study is being done to evaluate the safety and efficacy of pembrolizumab (MK-3475) in participants with advanced non-small cell lung cancer (NSCLC) tumors that are positive for programmed cell death ligand 1 (PD-L1): the hypothesis is that treatment with pembrolizumab will result in a clinically meaningful Overall Response Rate (ORR).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE Biological: Pembrolizumab
Intravenous infusion
Other Name: MK-3475
Study Arms  ICMJE Experimental: Pembrolizumab 10 mg/kg
Participants receive pembrolizumab 10 mg/kg intravenously over 30 minutes on Day 1 of each 21-day cycle for up to 2 years.
Intervention: Biological: Pembrolizumab
Publications * Nishio M, Takahashi T, Yoshioka H, Nakagawa K, Fukuhara T, Yamada K, Ichiki M, Tanaka H, Seto T, Sakai H, Kasahara K, Satouchi M, Han SR, Noguchi K, Shimamoto T, Kato T. KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer. Cancer Sci. 2019 Mar;110(3):1012-1020. doi: 10.1111/cas.13932. Epub 2019 Feb 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 13, 2016)
38
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2013)
24
Actual Study Completion Date  ICMJE March 31, 2017
Actual Primary Completion Date July 9, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is PD-L1 positive per central laboratory review
  • At least one measurable lesion
  • Radiographic progression of NSCLC after treatment with a platinum-containing doublet for Stage IIIB/IV or recurrent disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Scale 0 or 1
  • Adequate organ function

Exclusion Criteria:

  • Systemic cytotoxic chemotherapy, biological therapy, or major surgery within 3 weeks of the first dose of trial treatment
  • Systemic steroid therapy within 3 days prior to the first dose of trial treatment or any other form of immunosuppressive medication
  • Expected to require any other form of systemic or localized antineoplastic therapy while on trial
  • History of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer
  • Active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active autoimmune disease or documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
  • Concurrent or past history of interstitial lung disease
  • Pregnant or breast-feeding, or expecting to conceive or father children within the projected duration of the study, starting with screening visit through 120 days after the last dose of pembrolizumab
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Japan
 
Administrative Information
NCT Number  ICMJE NCT02007070
Other Study ID Numbers  ICMJE 3475-025
142500 ( Registry Identifier: JAPIC-CTI )
MK-3475-025 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP