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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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02142738
First received: May 16, 2014
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

This is an efficacy and safety study to assess 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 platinum-based chemotherapies.


Condition Intervention Phase
Non-Small-Cell Lung Carcinoma
Drug: Pembrolizumab
Drug: Paclitaxel
Drug: Carboplatin
Drug: Pemetrexed
Drug: Cisplatin
Drug: Gemcitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall Response Rate (ORR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: August 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 or until documented PD.
Drug: Pembrolizumab
Pembrolizumab IV solution
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 the remainder of the study or until documented PD. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
Drug: Paclitaxel
Paclitaxel IV solution
Drug: Carboplatin
Carboplatin IV solution
Drug: Pemetrexed
Pemetrexed IV solution
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. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
Drug: Carboplatin
Carboplatin IV solution
Drug: Pemetrexed
Pemetrexed IV solution
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. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
Drug: Pemetrexed
Pemetrexed IV solution
Drug: Cisplatin
Cisplatin IV solution
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. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
Drug: Carboplatin
Carboplatin IV solution
Drug: Gemcitabine
Gemcitabine IV solution
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. If PD occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented PD.
Drug: Cisplatin
Cisplatin IV solution
Drug: Gemcitabine
Gemcitabine IV solution

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 PD occurs. For the SOC chemotherapy participants, If documented PD occurs, these participants may be eligible for the Cross-Over Phase. Cross-Over Phase: This is only applicable for participants randomized to SOC who have documented PD. Participants will be treated with pembrolizumab for the remainder of the study or until PD occurs.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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
  • 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
  • Pregnant or breastfeeding, or expecting to conceive or father children during the study and through 120 days after last dose of study drug
  • Immediate family member who is investigational site or sponsor staff directly involved with this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02142738

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 27 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02142738     History of Changes
Other Study ID Numbers: 3475-024, 2014-000323-25
Study First Received: May 16, 2014
Last Updated: November 11, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Cisplatin
Gemcitabine
Paclitaxel
Pemetrexed
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014