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Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/KEYNOTE-024)

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: NCT02142738
Recruitment Status : Active, not recruiting
First Posted : May 20, 2014
Results First Posted : July 7, 2017
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 16, 2014
First Posted Date  ICMJE May 20, 2014
Results First Submitted Date April 14, 2017
Results First Posted Date July 7, 2017
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE August 25, 2014
Actual Primary Completion Date May 9, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2017)
Progression Free Survival (PFS) Rate at Month 6 [ Time Frame: Month 6 ]
PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment. The PFS rate at Month 6 was calculated.
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2014)
Progression Free Survival (PFS) [ Time Frame: Up to 2 years ]
Change History Complete list of historical versions of study NCT02142738 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2017)
  • Overall Survival (OS) Rate at Month 6 [ Time Frame: Month 6 ]
    OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. In those instances where participants were confirmed to be alive on the visit cut-off date of 09 May 2016, survival was censored as of 09 May 2016. The OS rate at Month 6 was calculated.
  • Objective Response Rate (ORR) [ Time Frame: Through data cutoff data of 09 May 2016 (Up to approximately 1.6 years) ]
    ORR was defined as the percentage of participants in the analysis population who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. The ORR through the data cutoff date of 09 May 2016 is presented for each treatment group.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2014)
  • Overall Survival (OS) [ Time Frame: Up to 2 years ]
  • Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/KEYNOTE-024)
Official Title  ICMJE A Randomized Open-Label Phase III Trial of MK-3475 Versus Platinum Based Chemotherapy in 1L Subjects With PD-L1 Strong Metastatic Non-Small Cell Lung Cancer
Brief Summary

This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies in the treatment of participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1) strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with pembrolizumab than when treated with SOC platinum-based chemotherapies.

With Amendment 09 (20 December 2017), once participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.

Detailed Description

Treatment Phase: Participants randomized to pembrolizumab will be treated for up to 35 cycles or until documented progressive disease (PD) occurs. Participants randomized to SOC chemotherapies will be treated with their randomized study drug for up to 4-6 cycles. After this, participants with non-squamous histologies may choose to be treated with maintenance pemetrexed for the remainder of the study or until disease progression, unacceptable adverse event(s) (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the participant, noncompliance with study treatment or procedures requirements, the participant receives 35 treatments of study treatment (pembrolizumab arm only), or administrative reasons. Participants receiving pembrolizumab who stop drug administration after receiving 35 study treatments for reasons other than disease progression or intolerability, or participants who attain a complete response and stop study treatment may be eligible for retreatment with pembrolizumab upon experiencing disease progression. The decision to retreat with a second course of pembrolizumab will be at the discretion of the Investigator only if participants meet the criteria for retreatment and the study is ongoing. Retreatment (second course) is limited to 17 cycles. Participants randomized to receive SOC chemotherapy may be eligible to receive pembrolizumab if crossover criteria are met.

Cross-Over Phase: This is only applicable for participants randomized to receive SOC. Eligible participants will be treated with pembrolizumab for the remainder of the study or until disease progression, unacceptable AEs, intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the participant, noncompliance with study treatment or procedures requirements, the participant receives 35 treatments of study treatment (pembrolizumab arm only), or administrative reasons.

Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Carcinoma
Intervention  ICMJE
  • Drug: Pembrolizumab
    Pembrolizumab IV solution
    Other Names:
    • MK-3475
    • SCH 900475
    • KEYTRUDA®
  • Drug: Paclitaxel
    Paclitaxel IV solution
  • Drug: Carboplatin
    Carboplatin IV solution
  • Drug: Pemetrexed
    Pemetrexed IV solution
  • Drug: Cisplatin
    Cisplatin IV solution
  • Drug: Gemcitabine
    Gemcitabine IV solution
Study Arms
  • Experimental: Pembrolizumab
    Participants receive pembrolizumab 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.
    Intervention: Drug: Pembrolizumab
  • Active Comparator: Paclitaxel+Carboplatin
    Participants receive paclitaxel 200 mg/m^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
    Interventions:
    • Drug: Paclitaxel
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Active Comparator: Pemetrexed+Carboplatin
    Participants receive pemetrexed 500 mg/m^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
    Interventions:
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Active Comparator: Pemetrexed+Cisplatin
    Participants receive pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 Q3W maintenance for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
    Interventions:
    • Drug: Pemetrexed
    • Drug: Cisplatin
  • Active Comparator: Gemcitabine+Carboplatin
    Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
    Interventions:
    • Drug: Carboplatin
    • Drug: Gemcitabine
  • Active Comparator: Gemcitabine+Cisplatin
    Participants receive gemcitabine 1250 mg/m^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and cisplatin 75 mg/m^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.
    Interventions:
    • Drug: Cisplatin
    • Drug: Gemcitabine
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 17, 2016)
305
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2014)
300
Estimated Study Completion Date May 29, 2020
Actual Primary Completion Date May 9, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received no prior systemic chemotherapy treatment for their metastatic NSCLC
  • At least one radiographically measurable lesion per RECIST 1.1
  • Life expectancy of at least 3 months
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
  • Adequate organ function
  • No 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, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
  • Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor at the time of or AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated
  • PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory
  • Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential
  • Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for 120 days after last dose of study drug and up to 180 days after last dose of chemotherapy

Exclusion Criteria:

  • EGFR sensitizing mutation and/or ALK translocation
  • Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
  • Currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of first dose of study drug
  • Tumor specimen is not evaluable for PD-L1 expression by the central laboratory
  • Receiving systemic steroid therapy <= 3 days prior to first dose of study drug or receiving any other form of immunosuppressive medication
  • Expected to require any other form of systemic or localized antineoplastic therapy during the study
  • Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery within 3 weeks of first dose of study drug; received thoracic radiation therapy of > 30 gray (Gy) within 6 months of first dose of study drug
  • Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Allogenic tissue/solid organ transplant
  • Interstitial lung disease or pneumonitis that has required oral or IV steroids
  • Received or will receive a live vaccine within 30 days prior to first dose of study drug
  • Active infection requiring IV systemic therapy
  • Known history of human immunodeficiency virus (HIV)
  • Known active tuberculosis, or hepatitis B or C
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
  • Pregnant or breastfeeding, or expecting to conceive or father children during the study and through 120 days after last dose of pembrolizumab or 180 days after last dose of SOC chemotherapy
  • Immediate family member who is investigational site or sponsor staff directly involved with this study
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Austria,   Belgium,   Canada,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Netherlands,   New Zealand,   Spain,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02142738
Other Study ID Numbers  ICMJE 3475-024
2014-000323-25 ( EudraCT Number )
142728 ( Registry Identifier: JAPIC )
MK-3475-024 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/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 January 2019

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