Back to resultsStudy of Two Doses of Pembrolizumab (MK-3475) Versus Docetaxel in Previously Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/KEYNOTE-010)
Primary Purpose
Non Small Cell Lung Cancer (NSCLC)
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pembrolizumab
Docetaxel
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer (NSCLC) focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
Inclusion Criteria:
- Life expectancy of at least 3 months
- Histologically- or cytologically-confirmed diagnosis of NSCLC that is anti-programmed cell death ligand 1 (PD-L1) positive per central laboratory review
- At least one bi-dimensional measurable lesion
- Radiographic progression after treatment with at least 2 cycles of a platinum-containing doublet
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Exclusion Criteria:
- Prior therapy with docetaxel for NSCLC
- Receiving systemic steroid therapy within 3 days prior to the first dose of study treatment or receiving any other form of immunosuppressive medication
- Currently participating or has participated in a study using an investigational antineoplastic agent or device within 30 days of first dose
- Expected to require any other form of systemic or localized antineoplastic therapy while on trial
- History of allogeneic tissue/solid organ transplant
- Prior systemic cytotoxic chemotherapy, antineoplastic biological therapy (e.g., cetuximab), major surgery within 3 weeks of the first dose of study drug; received thoracic radiation therapy of >30 Gy within 6 months of the first dose of study drug; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of study drug
- Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways), or took part in another pembrolizumab trial
- Known 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 cervical cancer, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
- Interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment
- Known history or active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after last dose of pembrolizumab or 180 days after last dose of docetaxel
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Pembrolizumab 2 mg/kg
Pembrolizumab 10 mg/kg
Docetaxel 75 mg/m^2
Arm Description
Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years.
Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years.
Outcomes
Primary Outcome Measures
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 September (Sep) 2015.
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Percentage of Participants Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, 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 of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Percentage of Participants Discontinuing Study Drug Due to AEs
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, 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 of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Secondary Outcome Measures
Overall Response Rate (ORR) by RECIST 1.1
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 of diameters) based on blinded independent central radiologists' review using RECIST 1.1. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Duration of Response (DOR) by RECIST 1.1
DOR is measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that death or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method and is reported in weeks. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Full Information
NCT ID
NCT01905657
First Posted
July 18, 2013
Last Updated
September 13, 2021
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01905657
Brief Title
Study of Two Doses of Pembrolizumab (MK-3475) Versus Docetaxel in Previously Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/KEYNOTE-010)
Official Title
A Phase II/III Randomized Trial of Two Doses of MK-3475 (SCH900475) Versus Docetaxel in Previously Treated Subjects With Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
August 9, 2013 (Actual)
Primary Completion Date
September 30, 2015 (Actual)
Study Completion Date
September 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study compared two doses of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) who had experienced disease progression after platinum-containing systemic therapy. Participants were assigned randomly to receive either pembrolizumab 2 mg/kg once every three weeks (Q3W), pembrolizumab 10 mg/kg Q3W or docetaxel 75 mg/m^2 Q3W. The total number of participants randomized depended upon demonstration of sufficient objective responses at an interim analysis.
Eligible participants who were allocated to the first course of pembrolizumab (2 mg/kg Q3W or 10 mg/kg Q3W) and experienced disease progression, to be permitted to receive a second course of pembrolizumab as long as Inclusion/Exclusion criteria were met.
Protocol Amendment 12 (effective date: 09 Dec 2015) enabled eligible participants who were allocated to docetaxel and experienced disease progression, to be permitted to switch over to receive pembrolizumab 2 mg/kg Q3W as long as Inclusion/Exclusion criteria were met.
With Protocol Amendment 15 (effective date: 03 Jan 2018), all second course and switch over participants will receive pembrolizumab 200 mg Q3W. Response or progression during the second and switch over pembrolizumab courses will not count towards efficacy outcome measures, and adverse events during the second and switch over pembrolizumab courses will not count towards safety outcome measures.
Also with Amendment 15, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and enrolled in an extension study (Keynote 587; NCT03486873) to continue protocol-defined assessments and treatment. Switch over participants who have not transitioned to pembrolizumab will be considered for the extension study on a case-by-case basis.
The primary study hypotheses are that pembolizumab prolongs Overall Survival (OS) and Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by independent radiologists' review in previously-treated participants with NSCLC in the strongly positive programmed cell death ligand 1 (PD-L1) stratum compared to docetaxel and in participants whose tumors express PD-L1 compared to docetaxel.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer (NSCLC)
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1034 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab 2 mg/kg
Arm Type
Experimental
Arm Description
Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years.
Arm Title
Pembrolizumab 10 mg/kg
Arm Type
Experimental
Arm Description
Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years.
Arm Title
Docetaxel 75 mg/m^2
Arm Type
Active Comparator
Arm Description
Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
TAXOTERE®
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 September (Sep) 2015.
Time Frame
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Title
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description
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. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Title
Percentage of Participants Experiencing Adverse Events (AEs)
Description
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, 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 of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Title
Percentage of Participants Discontinuing Study Drug Due to AEs
Description
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, 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 of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) by RECIST 1.1
Description
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 of diameters) based on blinded independent central radiologists' review using RECIST 1.1. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
Title
Duration of Response (DOR) by RECIST 1.1
Description
DOR is measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that death or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method and is reported in weeks. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame
Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Life expectancy of at least 3 months
Histologically- or cytologically-confirmed diagnosis of NSCLC that is anti-programmed cell death ligand 1 (PD-L1) positive per central laboratory review
At least one bi-dimensional measurable lesion
Radiographic progression after treatment with at least 2 cycles of a platinum-containing doublet
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Exclusion Criteria:
Prior therapy with docetaxel for NSCLC
Receiving systemic steroid therapy within 3 days prior to the first dose of study treatment or receiving any other form of immunosuppressive medication
Currently participating or has participated in a study using an investigational antineoplastic agent or device within 30 days of first dose
Expected to require any other form of systemic or localized antineoplastic therapy while on trial
History of allogeneic tissue/solid organ transplant
Prior systemic cytotoxic chemotherapy, antineoplastic biological therapy (e.g., cetuximab), major surgery within 3 weeks of the first dose of study drug; received thoracic radiation therapy of >30 Gy within 6 months of the first dose of study drug; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of study drug
Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways), or took part in another pembrolizumab trial
Known 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 cervical cancer, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
Interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment
Known history or active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after last dose of pembrolizumab or 180 days after last dose of docetaxel
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
26712084
Citation
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Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trial Information
Learn more about this trial
Study of Two Doses of Pembrolizumab (MK-3475) Versus Docetaxel in Previously Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/KEYNOTE-010)
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