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Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189 / KEYNOTE-189)

Trial Status: Closed to Accrual

This is an efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed / platinum chemotherapy versus pemetrexed / platinum chemotherapy alone in participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned to receive pembrolizumab combined with pemetrexed / platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed / platinum (Investigators choice of cisplatin or carboplatin). With Amendment 10 (effective date: 23-Dec-2019), active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded, and all participants in the 'control' arm will discontinue saline placebo. The primary hypothesis is that pembrolizumab in combination with pemetrexed / platinum chemotherapy prolongs Progression-Free Survival (PFS) and Overall Survival (OS) compared to pemetrexed / platinum chemotherapy alone.

Inclusion Criteria

  • Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC.
  • Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated.
  • Has measurable disease.
  • Has not received prior systemic treatment for their advanced/metastatic NSCLC.
  • Can provide tumor tissue.
  • Has a life expectancy of at least 3 months.
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
  • Has adequate organ function
  • If female of childbearing potential, is willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.
  • If male with a female partner(s) of child-bearing potential, must agree to use adequate contraception starting with the first dose of study medication through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.

Exclusion Criteria

  • Has predominantly squamous cell histology NSCLC.
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
  • Before the first dose of study medication: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy (e.g., erlotinib, crizotinib, cetuximab), c) Had major surgery (<3 weeks prior to first dose)
  • Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study medication.
  • Completed palliative radiotherapy within 7 days of the first dose of study medication.
  • Is expected to require any other form of antineoplastic therapy while on study.
  • Received a live-virus vaccination within 30 days of planned start of study medication.
  • Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis.
  • Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
  • Known sensitivity to any component of cisplatin, carboplatin or pemetrexed.
  • Has active autoimmune disease that has required systemic treatment in past 2 years.
  • Is on chronic systemic steroids.
  • Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
  • Is unable or unwilling to take folic acid or vitamin B12 supplementation.
  • Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab study and has been treated with pembrolizumab.
  • Has an active infection requiring therapy.
  • Has known history of Human Immunodeficiency Virus (HIV).
  • Has known active Hepatitis B or C.
  • Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
  • Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
  • Has symptomatic ascites or pleural effusion.
  • Has interstitial lung disease or a history of pneumonitis that required oral of IV glucocorticoids to assist with management.
  • Is pregnant or breastfeeding, or expecting to conceive or father children prior to 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
San Francisco
UCSF Medical Center-Mount Zion
Status: CLOSED_TO_ACCRUAL

Florida

Tampa
Moffitt Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Contact: Daniel Botelho Costa
Phone: 617-667-9925
Brigham and Women's Hospital
Status: ACTIVE
Contact: Mark Awad
Phone: 877-442-3324
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Mark Awad
Phone: 877-442-3324
Massachusetts General Hospital Cancer Center
Status: CLOSED_TO_ACCRUAL

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: CLOSED_TO_ACCRUAL

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: COMPLETED

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: ACTIVE
New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: CLOSED_TO_ACCRUAL
Contact: Leena Gandhi
Phone: 877-442-3324

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: CLOSED_TO_ACCRUAL

South Carolina

Charleston
Medical University of South Carolina
Status: COMPLETED

Virginia

Charlottesville
University of Virginia Cancer Center
Status: CLOSED_TO_ACCRUAL

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Merck and Company Inc

  • Primary ID 3475-189
  • Secondary IDs NCI-2015-02271, 163421, 2015-003694-15, MK-3475-189, s16-01055
  • Clinicaltrials.gov ID NCT02578680