Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02578680
First received: October 15, 2015
Last updated: February 22, 2017
Last verified: February 2017
  Purpose

This is an efficacy and safety study of pembrolizumab (MK-3475) combined with platinum-pemetrexed chemotherapy versus platinum-pemetrexed chemotherapy alone in participants with advanced or metastatic non-squamous 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 and platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed and platinum (Investigators choice of cisplatin or carboplatin).

The primary hypothesis is that pembrolizumab in combination with platinum-pemetrexed chemotherapy prolongs Progression Free Survival (PFS) compared to platinum-pemetrexed chemotherapy alone.


Condition Intervention Phase
Non-Small-Cell Lung Carcinoma
Biological: Pembrolizumab 200 mg
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Dietary Supplement: Folic acid 350-1000 μg
Dietary Supplement: Vitamin B12 1000 μg
Drug: Dexamethsone 4 mg
Drug: Saline solution
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Phase III Study of Platinum+ Pemetrexed Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-189)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging [ Time Frame: Up to 24 months ]

Secondary Outcome Measures:
  • Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging [ Time Frame: Up to 24 months ]
  • Overall Survival (OS) [ Time Frame: Up to 24 months ]
  • Progression Free Survival (PFS) as Assessed by Investigator Immune-related RECIST (irRECIST) Response Criteria [ Time Frame: Up to 24 months ]

Estimated Enrollment: 570
Study Start Date: January 2016
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 (with vitamin supplementation) IV PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 every 3 weeks (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Biological: Pembrolizumab 200 mg
IV infusion
Drug: Cisplatin
IV infusion
Drug: Carboplatin
IV infusion
Drug: Pemetrexed
IV infusion
Dietary Supplement: Folic acid 350-1000 μg
Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.
Dietary Supplement: Vitamin B12 1000 μg
Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.
Drug: Dexamethsone 4 mg
For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.
Active Comparator: Control
Participants receive saline placebo IV PLUS pemetrexed 500 mg/m^2 (with vitamin supplementation) IV PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 Q3W for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. If progression occurs, participants may be able to receive pembrolizumab Q3W for the remainder of the study or until documented progression.
Drug: Cisplatin
IV infusion
Drug: Carboplatin
IV infusion
Drug: Pemetrexed
IV infusion
Dietary Supplement: Folic acid 350-1000 μg
Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.
Dietary Supplement: Vitamin B12 1000 μg
Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.
Drug: Dexamethsone 4 mg
For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.
Drug: Saline solution
IV infusion

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV non-squamous 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 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, or abdominal 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 or 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.
  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: NCT02578680

  Show 63 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02578680     History of Changes
Other Study ID Numbers: 3475-189
2015-003694-15 ( EudraCT Number )
163421 ( Registry Identifier: JAPIC-CTI )
Study First Received: October 15, 2015
Last Updated: February 22, 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1
Non-Small-Cell Lung Cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Vitamins
Folic Acid
Vitamin B 12
Hydroxocobalamin
Pembrolizumab
Carboplatin
Cisplatin
Pemetrexed
Vitamin B Complex
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Hematinics

ClinicalTrials.gov processed this record on April 27, 2017