Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I Study of Single Agent Pembrolizumab (MK-3475) in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma (KEYNOTE 001)
Brief Summary: The present study has 5 parts. In Parts A and A1, the dose of intravenous (IV) pembrolizumab (MK-3475) will be escalated from 1 to 10 mg/kg to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for participants with a histologically- or cytologically-confirmed diagnosis of any type of carcinoma or melanoma (MEL) by evaluating the Dose Limiting Toxicities (DLTs). Following completion of the dose escalation, additional patients will be enrolled in Part A2 to further define pharmacokinetic characteristics. Part B of the study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL and compare every 2 week dosing (Q2W) to every 3 week dosing (Q3W). Part C of the study will investigate the safety, tolerability, and efficacy of pembrolizumab administered at 10 mg/kg Q3W in participants with non-small cell lung carcinoma (NSCLC) that is locally advanced or metastatic. Part D of the study will investigate the low and high doses of study drug identified in Parts A and B (2 mg/kg and 10 mg/kg) administered Q3W in participants with advanced or metastatic MEL. Part E (closed with Amendment 7) was planned to investigate low, medium, and high doses of pembrolizumab in combination with standard chemotherapy in participants with locally advanced or metastatic NSCLC. Part F will investigate low and high doses of pembrolizumab (2 mg/kg and 10 mg/kg) administered Q2W or Q3W in treatment-naive and previously-treated participants with NSCLC with programmed cell death 1 ligand (PD-L1) gene expression. The primary hypotheses are the following: that pembrolizumab will have acceptable safety and tolerability; that pembrolizumab will show a clinically meaningful response rate (RR) or disease-control rate (DCR) in participants with melanoma (ipilimumab-refractory or not) and NSCLC, and that pembrolizumab will show a more clinically meaningful RR in participants with either cancer whose tumors express PD-L1.


Options:
A: Inclusion Criteria

* In Part A: Histological or cytological diagnosis of MEL or any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. In Parts B and D of the study, histological or cytological diagnoses of metastatic MEL with progressive locally advanced or metastatic disease. In Parts C and F, histological or cytological diagnosis of NSCLC. In Part F1, participants with Stage IV NSCLC without prior systemic therapy may be eligible.
* Failure of established standard medical anti-cancer therapies for a given tumor type or intolerance to such therapy.
* In Parts B, C, D, or F of the study, MEL or NSCLC must be measurable by imaging.
* In Part F of the study, NSCLC with PD-L1 gene expression.
* Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
* Adequate organ function.
* Female participants of childbearing potential should have a negative urine or serum pregnancy test prior to receiving study medication
* Female participants of childbearing potential must be willing to use adequate contraception from study start, through the course of the study, and for 120 days after the last dose of study medication
* Male participants of childbearing potential must agree to use adequate contraception from the first dose of study medication through 120 days after the last dose of study medication

Exclusion Criteria

* Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events caused by therapy administered more than 4 weeks prior to first dose.
* Participation in a study of an investigational agent or using an investigational device within 30 days of administration of pembrolizumab, with the exception of participants in the follow-up phase.
* Other form(s) of antineoplastic therapy anticipated during the period of the study.
* History of non-infectious pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
* Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication, excepting use of inhaled steroids.
* Risk factors for bowel obstruction or bowel perforation (including a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis).
* History of a hematologic malignancy, malignant primary brain tumor, malignant sarcoma, or another malignant primary solid tumor, unless no evidence of that disease for 5 years.
* Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Previous severe hypersensitivity reaction to another monoclonal antibody (mAb).
* Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents, except vitiligo or resolved childhood asthma/atopy.
* Prior therapy with another anti-programmed cell death (PD)-1 agent or previously enrolled in any pembrolizumab trial.
* Active infection requiring therapy.
* Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen \[HBsAg\] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid \[HCV RNA\] (qualitative) is detected).
* Regular use of illicit drugs or a recent history (within the last year) of substance abuse (including alcohol).
* Symptomatic ascites or pleural effusion.
* Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
B: Inclusion Criteria:

* Men and Women ≥ 18 years of age
* Diagnosed with stage IV Non-Small Cell Lung Cancer
* Diagnosed with recurrent stage IIIB non-small cell lung cancer and failed previous concurrent chemoradiation with no further curative options.

Exclusion Criteria:

* Subjects with untreated CNS metastases are excluded.
* Subjects with carcinomatous meningitis
* Subjects with an active, known or suspected autoimmune disease.
* Subjects with a condition requiring systemic treatment with either corticosteroids ( \> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.
* Women who are pregnant, plan to become pregnant, and/or breastfeed during the study.

Other protocol defined inclusion/exclusion criteria apply
C: Inclusion Criteria:

* Men \& women ≥18 years of age
* Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for advanced disease
* Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
* Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

Exclusion Criteria:

* Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10mg daily prednisone (or equivalent)
* Subjects with carcinomatous meningitis
* Subjects with active or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll
* Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
* Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), 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)
* Prior treatment with Docetaxel
* Treatment with any investigational agent within 14 days of first administration of study treatment

Other protocol-defined inclusion/exclusion criteria apply
D: Inclusion Criteria for the Induction Phase:

* You must sign an informed consent document for clinical research.
* You must have Stage IIIB or IV nonsquamous Non-Small Cell Lung Cancer.
* You must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work.
* You are allowed to have had prior radiation therapy as long as it was not to more than 25% of the bone marrow and did not include the whole pelvis. Thoracic radiation must be completed more than 30 days before the study. You must be recovered from the toxic effects (except hair loss).
* You must have at least 1 measurable tumor lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated by computed tomography (CT) Scan.
* Your test results assessing the function of your blood forming tissue, kidneys, and liver must be satisfactory.
* You must be 18 years of age or older.
* Women must be sterile, postmenopausal or on contraception and men must be on contraception or sterile (e.g. post-vasectomy).

Exclusion Criteria for the Induction Phase:

* You cannot have squamous cell and/or mixed small cell, non-small cell lung cancer
* You cannot have received other investigational drugs within the last 30 days of entering the trial.
* You cannot have previously completed or withdrawn from this study or any other study investigating pemetrexed.
* You cannot have other serious on-going illnesses including active infections.
* You cannot have a serious cardiac condition, such as a heart attack, angina, or heart disease within 6 months of entering the trial.
* You cannot have had another form of cancer other than superficial basal cell and superficial squamous (skin) cell cancer, or carcinoma in situ of the cervix within the last 5 years. Patients with a history of low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years ago.
* You cannot have known central nervous system (CNS) metastases, other than treated, stable brain metastasis.
* You cannot be receiving nor have received any prior systemic anticancer therapy for lung cancer (including chemotherapy given after surgery in early-stage treatment).
* You cannot have clinically significant third-space fluid collections (e.g. ascites or pleural effusions that cannot be controlled by drainage or other procedures).
* You cannot have received a recent (within 30 days) or are receiving a yellow fever vaccination.
* You are unable to stop taking more than 1.3 grams of aspirin on a daily basis or other non-steroidal anti-inflammatory drugs (NSAIDs).
* You are unable or unwilling to take folic acid, injections of vitamin B12, or corticosteroids.
* You cannot be pregnant or breastfeeding.

Inclusion criteria at Randomization for the Maintenance Phase:

* You must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work.
* You must have documented radiographic evidence of a tumor response of complete response (CR), partial response (PR), or stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Tumor assessment must occur between Cycle 4 (Day 1) of induction therapy and the date of randomization. This response does not have to be confirmed in order for the patient to be randomized to the maintenance phase.

Answer: A