Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With Tyrosine Kinase Inhibitor- (TKI)-Resistant Epidermal Growth Factor Receptor- (EGFR)-Mutated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-789/KEYNOTE-789)

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC.

- Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R.

- Investigator-determined radiographic disease progression per RECIST 1.1 after
treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd
generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed
documented absence of EGFR T790M mutation; b) Participants with confirmed acquired
T790M mutation after 1st or 2nd generation EGFR TKI (e.g.
erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure
prior to enrollment; c) Participants previously failed osimertinib TKI treatment as
1st line therapy are eligible regardless of their EGFR T790M mutation status. Note:
TKI washout period for all participants is 1 week or 2 half-lives after last treatment
dose, whichever is longer. TKI washout should be completed prior to first dose of
study treatment.

- Measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology.

- Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy
since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated.

- Life expectancy of at least 3 months.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days
prior to the first dose of study treatment but before randomization.

- Male participants must agree to use contraception during the treatment period and for
at least 120 days after the last dose of pembrolizumab and up to 180 days after last
dose of chemotherapeutic agents.

- Female participants must not be pregnant, not breastfeeding, and must agree to use
contraception during the treatment period and for at least 120 days after the last
dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic
agents.

- Adequate organ function.

Exclusion Criteria:

- Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the
predominant cell type; if small cell elements are present, the participant is
ineligible.

- Symptomatic ascites or pleural effusion. A participant who is clinically stable
following treatment for these conditions (including therapeutic thoraco- or
paracentesis) is eligible.

- Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic
T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137).

- Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding
EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior 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 NSCLC. 2) If
participant received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study treatment.
3) Prior exposure to traditional medicine(s) is allowed as long as therapy was
discontinued at least 4 weeks prior to the first dose of study treatment.]

- Received prior radiotherapy within 2 weeks of start of study treatment or has received
lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study
treatment. Participants must have recovered from all radiation-related toxicities, not
require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous
system (CNS) disease.

- Received a live vaccine within 30 days prior to the first dose of study treatment.

- Currently participating in or has participated in a study of an investigational agent
or has used an investigational device within 4 weeks prior to the first dose of study
treatment.

- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study treatment.

- Known additional malignancy that is progressing or has required active treatment
within the past 5 years. (Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ
(e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially
curative therapy are not excluded.)

- Known active untreated CNS metastases and/or carcinomatous meningitis.

- Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.

- Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.

- Active autoimmune disease that has required systemic treatment in past 2 years.

- History of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.

- Active infection requiring systemic therapy.

- Known history of human immunodeficiency virus (HIV) infection.

- Known history of Hepatitis B or known active Hepatitis C virus.

- Known history of active tuberculosis (TB; Bacillus tuberculosis)

- Pregnant, breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of pembrolizumab and up to 180 days after the last dose of
chemotherapeutic agents.