Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Open-Label Phase III Trial of Pembrolizumab Versus Platinum Based Chemotherapy in 1L Subjects With PD-L1 Strong Metastatic Non-Small Cell Lung Cancer
Brief Summary: This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies in the treatment of participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1) strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with pembrolizumab than when treated with SOC platinum-based chemotherapies.

With Amendment 09 (20 December 2017), once participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.


Options:
A: 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.
B: Inclusion Criteria:

* Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received no prior systemic chemotherapy treatment for their metastatic NSCLC
* At least one radiographically measurable lesion per RECIST 1.1
* Life expectancy of at least 3 months
* Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
* Adequate organ function
* No history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
* Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor at the time of or AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated
* PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory
* Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential
* Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for 120 days after last dose of study drug and up to 180 days after last dose of chemotherapy

Exclusion Criteria:

* EGFR sensitizing mutation and/or ALK translocation
* Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of 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 disease.
* Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of study drug
* Tumor specimen is not evaluable for PD-L1 expression by the central laboratory
* Receiving systemic steroid therapy \< 3 days prior to first dose of study drug or receiving any other form of immunosuppressive medication
* Expected to require any other form of systemic or localized antineoplastic therapy during the study
* Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery within 3 weeks of first dose of study drug; received thoracic radiation therapy of \> 30 gray (Gy) within 6 months of first dose of study drug
* Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor \[TNFR\] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
* Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active autoimmune disease that has required systemic treatment in past 2 years
* Allogenic tissue/solid organ transplant
* Interstitial lung disease or pneumonitis that has required oral or IV steroids
* Received or will receive a live vaccine within 30 days prior to first dose of study drug
* Active infection requiring IV systemic therapy
* Known history of human immunodeficiency virus (HIV)
* Known active tuberculosis, or hepatitis B or C
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
* Is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
* Pregnant or breastfeeding, or expecting to conceive or father children during the study and through 120 days after last dose of pembrolizumab or 180 days after last dose of SOC chemotherapy
* Immediate family member who is investigational site or sponsor staff directly involved with this study
C: Inclusion Criteria:

* Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer \[AJCC\] 7th edition) squamous NSCLC.
* Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
* Has not received prior systemic treatment for metastatic NSCLC.
* Has provided tumor tissue from locations not radiated prior to biopsy.
* 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 an adequate method of contraception for the course of the study through 180 days after the last dose of study drug.
* If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study drug through 95 days after the last dose of study drug. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Exclusion Criteria:

* Has non-squamous 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 drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has 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 drug.
* Completed palliative radiotherapy within 7 days of the first dose of study drug.
* Is expected to require any other form of antineoplastic therapy while on study.
* Has received a live-virus vaccination within 30 days of planned treatment start.
* Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.
* Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
* Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.
* Has active autoimmune disease that has required systemic treatment in past 2 years.
* Is on chronic systemic steroids.
* Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.
* Has participated in any other pembrolizumab trial 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. Active Hepatitis B.
* Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol).
* Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
D: Inclusion Criteria:

1. Age at least 18 years.
2. Documented evidence of NSCLC (locally advanced, unresectable, Stage III)
3. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.
4. World Health Organisation (WHO) Performance Status of 0 to 1.
5. Estimated life expectancy of more than 12 weeks.

Exclusion Criteria:

1. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
2. Active or prior autoimmune disease or history of immunodeficiency.
3. Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
4. Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
5. Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy.
6. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

Answer: B