Effect of Pembrolizumab With or Without Carboplatin and Paclitaxel on Immune Response in Patients With Recurrent or Stage IIIB-IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. Determine the immune effects of single agent pembrolizumab and pembrolizumab combined with
low-dose carboplatin and paclitaxel.

II. Estimate the treatment response to single agent pembrolizumab and pembrolizumab combined
with low-dose carboplatin and paclitaxel.

SECONDARY OBJECTIVES:

I. Determine the toxicity and tolerability of pembrolizumab and pembrolizumab combined with
low-dose carboplatin and paclitaxel.

II. Assess quality of life (QOL) in patients receiving single agent pembrolizumab and
pembrolizumab combined with carboplatin and paclitaxel.

III. Assess the association between immune response and clinical response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1.

ARM II: Patients receive pembrolizumab IV over 30 minutes on day 1, paclitaxel IV over 1 hour
and carboplatin IV over 1 hour on days 1, 7 and 14.

In both arms, courses repeat every 3 weeks for 2 years in the absence of disease progression
or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days and then
every 8 weeks thereafter.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed non-small cell lung
cancer (NSCLC) that is advanced/metastatic (stage IIIB/IV) or recurrent (progression
after surgery or radiation or chemo-radiation treatment for loco-regional disease)

- Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on day 1; subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived specimen only upon agreement from the sponsor; at least 4 mm of tumor tissue
will be needed for programmed cell death-ligand (PD-L1) staining

- Patients who have received up to two previous lines of systemic chemotherapy are
eligible for this trial

- At least one measurable lesion as defined by Response Evaluation Criteria in Solid
Tumors (RECIST) version (v)1.1 on screening computed tomography (CT) or magnetic
resonance imaging (MRI)

- Eastern Cooperative Oncology Group (ECOG) performance status of 2

- White blood cell count (WBC) > 2,500 cells/mcL

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 9 g/dL

- Total bilirubin =< 2.0 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x ULN Or =< 5 x ULN in presence of liver metastases

- Creatinine within normal institutional limits OR creatinine clearance > 50 mL/min for
patients with creatinine levels above institutional normal

- Potassium >= lower limit of normal

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) for the duration of study
participation and for 4 weeks after the final administration of study drugs; should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately

- Ability to understand and the willingness to sign an Institutional Review Board
(IRB)-approved informed consent document

Exclusion Criteria:

- Known active (untreated) central nervous system (CNS) metastases that require
steroids; subjects with CNS metastases who have completed a course of therapy would be
eligible for the study provided they are clinically stable for at least 4 weeks before
study entry, defined as:

- No evidence of new or enlarging CNS metastasis or new neurological symptoms
attributable to CNS metastases

- Asymptomatic and receiving either no or stable doses of anticonvulsants and no
corticosteroids for the 4 weeks prior to study entry

- Current or previous other malignancy within 2 years of study entry, except cured basal
or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial
neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy
without sponsor approval

- History of previous exposure to an anti-programmed cell death 1 (PD-1)/PD-L1 agent

- Patients receiving any other investigational agents and or more that two different
chemotherapy regimens for treatment of metastatic disease

- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
baseline) from adverse events due to a previously administered agent

- Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and
may qualify for the study

- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to pembrolizumab, paclitaxel or carboplatin

- Current uncontrolled cardiac disease such as angina or myocardial infarction,
congestive heart failure including New York Heart Association functional
classification of 3, or arrhythmia requiring treatment

- History of pneumonitis or active lung infection

- Chronic or current active infectious disease requiring systemic antibiotics,
antifungals, or antivirals

- Patients receiving chronic steroids and or immunosuppression

- Known human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) or
hepatitis C virus (HCV) viremia or at risk for HBV reactivation; HBV deoxyribonucleic
acid (DNA) and testing for HCV ribonucleic acid (RNA) must be undetectable; at risk
for HBV reactivation is defined as hepatitis B surface antigen positive or
anti-hepatitis B core antibody positive

- History of autoimmune disease(s)

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Any other condition or circumstance that could interfere with adherence to the study's
procedures or requirements, or otherwise compromise the study's objectives such as
history of, or any evidence of active, non-infectious pneumonitis

- Has an active infection requiring systemic therapy

- Pregnant women are excluded; breastfeeding should be discontinued prior to study entry