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

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ClinicalTrials.gov Identifier: NCT02007070
Recruitment Status : Completed
First Posted : December 10, 2013
Results First Posted : December 5, 2016
Last Update Posted : March 19, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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).

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Biological: Pembrolizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 28, 2014
Actual Primary Completion Date : July 9, 2015
Actual Study Completion Date : March 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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.
Biological: Pembrolizumab
Intravenous infusion
Other Name: MK-3475




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02007070


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02007070     History of Changes
Other Study ID Numbers: 3475-025
142500 ( Registry Identifier: JAPIC-CTI )
MK-3475-025 ( Other Identifier: Merck Protocol Number )
First Posted: December 10, 2013    Key Record Dates
Results First Posted: December 5, 2016
Last Update Posted: March 19, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents