Please select the eligibility criteria that correspond to the clinical trial below.
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)
Brief Summary: 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.

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.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following stage criteria:

  * Stage IIIB disease\* that is not suitable for radical radiotherapy
  * Stage IV disease\* NOTE: \*Radiographically verified
* At least 1 measurable lesion by clinical examination or radiography
* No mixed histologies of small cell lung cancer and NSCLC
* No clinically apparent brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* At least 12 weeks

Hematopoietic

* WBC ≥ 3,000/mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL

Hepatic

* AST \< 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Alkaline phosphatase \< 3 times ULN
* Bilirubin \< 1.5 times ULN

Renal

* Creatinine clearance ≥ 60 mL/min (by Wright equation) OR ≥ 70 mL/min (by \^51Cr-EDTA clearance)

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able and willing to participate in the quality of life assessment
* No pre-existing neuropathy \> grade 2
* No other malignancy that would preclude study treatment or study comparisons
* No evidence of severe or uncontrolled systemic disease, significant clinical disorder, or laboratory finding that would preclude study participation
* No psychiatric disorder that would preclude study participation
* No other condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy

Chemotherapy

* No prior chemotherapy, including neoadjuvant or adjuvant chemotherapy
* No other concurrent cytotoxic chemotherapy

Endocrine therapy

* No concurrent hormonal therapy except contraceptives or replacement steroids

Radiotherapy

* No prior radiotherapy

Surgery

* Recovered from prior surgery
* Prior surgical resection for NSCLC allowed

Other

* More than 12 weeks since prior investigational agents and recovered
* No other concurrent specific antitumor therapy
* No other concurrent investigational agents
B: 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.
C: Inclusion Criteria:

* adult patients, \>=18 years of age;
* documented inoperable, locally advanced, metastatic or recurrent non-squamous NSCLC;
* adequate liver and kidney function;
* women of childbearing potential must have a negative serum pregnancy test within 7 days of starting study treatment.

Exclusion Criteria:

* prior chemotherapy or treatment with another systemic cancer therapy;
* surgery (including open biopsy), significant traumatic injury, or radiotherapy within the last 4 weeks prior to first dose of study treatment;
* brain metastasis or spinal cord compression;
* fertile men, and women of childbearing potential, not using adequate contraception;
* treatment with any other investigational agent, or participation in another clinical trial, within 30 days prior to entering the study.
D: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed non-small cell lung cancer EXCEPT squamous cell carcinoma; mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible; cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy
* Patients must have advanced NSCLC (stage IIIB with malignant pleural effusion or stage IV or recurrent disease)
* Patients must have measurable or non-measurable disease
* ECOG performance status 0 or 1
* Patients must not have known central nervous system (CNS) metastases; a head CT is required within 4 weeks prior to study entry; (MRIs are also acceptable)
* Patients must not have received prior systemic chemotherapy at any time
* ANC \>= 1500/mm\^3
* Platelets \>= 100,000/mm\^3
* Total bilirubin =\< 1.5 mg/dl
* Transaminases =\< 5 x ULN
* Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN)
* Urine dipstick for proteinuria of less than 1+ (i.e., either 0 or trace); if urine dipstick is \>= 1+ then a 24 hour urine for protein must demonstrate \< 500 mg of protein in 24 hours to allow participation in the study; note: urinalysis is also acceptable
* Patients must have INR =\< 1.5 and a PTT no greater than upper limits of normal within 1 week prior to randomization
* Pregnant and lactating women are excluded from the study
* Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study
* Patients must not have had immuno, hormonal or radiation therapy within 3 weeks prior to entering the study; those who have not recovered from adverse events due to agents administered more than 3 weeks earlier are ineligible
* Patients must not have ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients must have no history of thrombotic or hemorrhagic disorders
* Patients with history of hypertension must be well-controlled (\< 150/100) on a stable regimen of anti-hypertensive therapy
* Patients must not be receiving chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed
* Patients must not have serious non-healing wound ulcer, or bone fracture, or major surgical procedure within 21 days prior to starting treatment
* Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation of venous access devices is allowed; caution should be taken on treating patients with low dose heparin or low molecular weight heparin for DVT prophylaxis during treatment with bevacizumab as there may be an increased risk of bleeding
* Patients with a history of gross hemoptysis (defined as bright red blood of a 1/2 teaspoon or more) will be excluded from this trial

Answer: B