A Multiple Antigen Vaccine (STEMVAC) for the Treatment of Patients With Stage IV Non-Small Cell Lung Cancer

Inclusion Criteria:

• Histologically-confirmed diagnosis of stage IV non-squamous or squamous NSCLC.

• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within one month of first vaccine. Target lesions situated in apreviously irradiated area are considered measurable if progression has beendemonstrated in such lesions.

• Have completed 3-4 cycles of chemoimmunotherapy, without evidence of progressivedisease. Pembrolizumab has to be included in at least 3 of these cycles.

• Have not received more than 2 cycles of maintenance pembrolizumab and/or pemetrexedand be a candidate for continuation of this therapy.

• At least 1 site of disease that could be biopsied during treatment. This site shouldnot be a site that is used to determine measurable disease for efficacy purposes.Lesions that will be biopsied should not be on a previously irradiated area unlessprogression has been demonstrated in such lesions.

• Patients must be at least 28 days post systemic steroids prior to enrollment, unlessthis is a steroid administered concurrently with chemotherapy or used as part ofprophylaxis to prevent intravenous (IV) contrast reactions.

• Patients must have Eastern Cooperative Oncology Group (ECOG) Performance StatusScore of 0 or 1.

• Patients must have recovered from major infections and/or surgical procedures, andin the opinion of a principle investigator (PI)/co-PI/study physician/physicianextender, not have any significant active concurrent medical illnesses precludingprotocol treatment.

• Willing to undergo up to two serial biopsies while on study.

• Estimated life expectancy of more than 6 months.

• White blood cells (WBC) >= 3000/mm^3 (within 60 days of first vaccination).

• Lymphocyte count >= 800/mm^3 (within 60 days of first vaccination).

• Platelet count >= 75,000/mm^3 (within 60 days of first vaccination).

• Hemoglobin (Hgb) >= 9 g/dl (within 60 days of first vaccination).

• Serum creatinine =< 1.2 mg/dl or creatinine clearance > 50 ml/min (within 60 days offirst vaccination).

• Total bilirubin =< 1.5 mg/dl (within 60 days of first vaccination).

• Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) =< 2times upper limit of normal (ULN) or SGOT =< 5 times upper limit of normal (ULN) inthe presence of liver metastasis (within 60 days of first vaccination).

• If female of childbearing potential has a negative urine or serum pregnancy testwithin 72 hours prior to receiving the first dose of study medication.

• All patients who are having sex that can lead to pregnancy must agree tocontraception for the duration of study.

• Patients must be at least 18 years of age.

Exclusion Criteria:

• Patients with any of the following cardiac conditions:

• Symptomatic restrictive cardiomyopathy

• Unstable angina within 4 months prior to enrollment

• New York Heart Association functional class III-IV heart failure on activetreatment

• Symptomatic pericardial effusion

• Patients with central nervous system (CNS) metastasis that have not been treated.Patients with previously treated brain metastases may participate provided they areclinically stable for at least 4 weeks and, have no evidence of new or enlargingbrain metastases and also are off steroids for 2 weeks prior to dosing with studymedication.

• Patients with any contraindication to receiving recombinant humangranulocyte-macrophage colony stimulating factor (rhuGM-CSF) based products.

• Patients with any clinically significant autoimmune disease that requires activetreatment with immunosuppressants. Replacement therapy (e.g., thyroxine, insulin) isnot considered a form of systemic treatment. Administration of systemic steroids (i.e., for allergic reactions, computed tomography (CT) scans, or the management ofimmune related adverse events [irAEs]) is allowed.

• Has a known history of another prior invasive malignancy within 2 years, exceptsubjects with early stage cancer that has undergone potentially curative therapywith no evidence of that disease recurrence for 2 years since initiation of thattherapy.

• Patients who are simultaneously enrolled in any other treatment study.

• Patients who are pregnant or breastfeeding.

• Patients with genetic driver alterations (e.g EGFR, ALK, ROS1, BRAF, MET ex 14, RET)for which targeted treatment exist and are Food and Drug Association (FDA) approved,except if the subject is not eligible or has progressed through those therapies.