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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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01905657
First received: July 18, 2013
Last updated: November 23, 2016
Last verified: November 2016
  Purpose

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. This study used an adaptive trial design so that the total number of participants randomized depended upon demonstration of sufficient objective responses at an interim analysis.

Based on the positive outcome of the Overall Survival (OS) analysis, Protocol Amendment 12 (effective date: 09 Dec 2015) enabled eligible participants who were allocated to docetaxel and experienced disease progression, to be permitted to crossover to receive pembrolizumab 2 mg/kg Q3W as long as Inclusion/Exclusion criteria were met. These participants were participating in the Cross-Over Phase.

The primary study hypotheses are that pembolizumab prolongs 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.


Condition Intervention Phase
Non Small Cell Lung Cancer (NSCLC)
Biological: Pembrolizumab
Drug: Docetaxel
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Through database cutoff date of 30 Sep 2015 (Approximately 23 months) ]
    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.

  • Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Through database cutoff date of 30 Sep 2015 (Approximately 23 months) ]
    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.

  • Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: AEs: Up to 30 days after last dose of study drug (Up to approximately 24 months). Serious AEs: Up to 90 days after last dose of study drug (Up to approximately 27 months). ]
    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 (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 after last dose of study drug (serious AEs were monitored for up to 90 days after last dose of study drug).

  • Percentage of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to approximately 23 months ]
    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 (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.


Secondary Outcome Measures:
  • Overall Response Rate (ORR) by RECIST 1.1 [ Time Frame: Through database cutoff date of 30 Sep 2015 (Approximately 23 months) ]
    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) based on blinded independent central radiologists' review using RECIST 1.1.

  • Duration of Response (DOR) by RECIST 1.1 [ Time Frame: Through database cutoff date of 30 Sep 2015 (Approximately 23 months) ]
    DOR is 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. DOR was analyzed using the Kaplan-Meier method and is reported in weeks.


Enrollment: 1034
Study Start Date: August 2013
Estimated Study Completion Date: March 2019
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab 2 mg/kg
Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years.
Biological: Pembrolizumab
Participants who experienced disease progression on docetaxel may have been eligible to crossover to receive pembrolizumab.
Other Names:
  • MK-3475
  • KEYTRUDA®
Experimental: Pembrolizumab 10 mg/kg
Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years.
Biological: Pembrolizumab
Participants who experienced disease progression on docetaxel may have been eligible to crossover to receive pembrolizumab.
Other Names:
  • MK-3475
  • KEYTRUDA®
Active Comparator: Docetaxel 75 mg/m^2
Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Participants who experienced disease progression, may have been eligible to crossover to receive pembrolizumab 2 mg/kg Q3W.
Biological: Pembrolizumab
Participants who experienced disease progression on docetaxel may have been eligible to crossover to receive pembrolizumab.
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Docetaxel
Participants who initially receive docetaxel may be eligible to crossover to receive pembrolizumab.
Other Name: TAXOTERE®

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01905657

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

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01905657     History of Changes
Other Study ID Numbers: 3475-010
2012-004391-19 ( EudraCT Number )
132355 ( Registry Identifier: Japic-CTI )
Study First Received: July 18, 2013
Results First Received: September 15, 2016
Last Updated: November 23, 2016

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
Docetaxel
Pembrolizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017