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)-Japan Extension Study
Condition: Non-Small-Cell Lung Carcinoma
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pembrolizumab 200 mg; Cisplatin; Carboplatin; Pemetrexed; Folic acid 350-1000 μg; Vitamin B12 1000 μg; Dexamethasone 4 mg; Saline solution
Intervention description: IV infusion; IV infusion; IV infusion; IV infusion; 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.; 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.; For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.; IV infusion
Intervention MeSH terms: Folic Acid; Vitamin B 12; Dexamethasone; Carboplatin; Pembrolizumab; Pemetrexed
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Non-Small-Cell Lung Cancer (NSCLC); PD1; PD-1; PDL1; PD-L1; Non-Small-Cell Lung Cancer

Summary:

      This is a Japan Extension Study of Global Study MK-3475-189 (NCT02578680). This is an
      efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed/platinum
      chemotherapy versus pemetrexed/platinum chemotherapy alone in adult Japanese 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 11 (effective date 31-Jan-2022), once the study objectives have been met or
      the study has ended, participants will be discontinued from this study and will be enrolled
      in an extension study to continue protocol-defined assessments and treatment.

      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.
    

Eligibility criteria:

        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 a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study.