FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer

Primary Objective

- To explore the efficacy of combining stereotactic body radiotherapy (SBRT) with FLT3
ligand immunotherapy for advanced non-small cell lung cancer (NSCLC).

Secondary Objectives

- To establish the feasibility and safety of combining SBRT with FLT3 ligand immunotherapy
for advanced NSCLC.

- To quantify and evaluate potential surrogate outcomes for clinical efficacy of this
treatment approach, including radiographic responses, immunologic responses, and
circulating tumor cell levels.

Inclusion Criteria:

- AJCC stage 3 or 4 histologically proven NSCLC not amenable to curative therapy

- Age >= 18 years

- Prior treatment with at least one standard chemotherapy regimen or targeted agent
prior to enrollment

- Radiological assessment within 21 days prior to study entry demonstrating measurable
disease that includes at least one pulmonary lesion . 1 cm in greatest dimension that
would be amenable to SBRT and at least one measurable lesion that would be outside of
the SBRT treatment fields

- History/physical examination within 30 days prior to registration

- ECOG performance status 0-2

- Signed, written informed consent

Exclusion Criteria:

- Less than 21 days between registration and the last receipt of chemotherapy,
biotherapy, immunotherapy, radiotherapy (excluding palliative radiotherapy), or major
surgery. Prior receipt of immunomodulatory therapy (eg: nivolumab) is permitted, as
long as there has been a 21 day washout period following the most recent treatment.

- Untreated central nervous system metastases. Patients with a history of brain
metastases must have had no CNS-directed therapy within the past 60 days and
radiological assessment within 30 days of study entry demonstrating a lack of
progressive CNS disease

- Ongoing or recent (within 21 days prior to study entry) use of high dose oral
corticosteroids (.2 mg of dexamethasone daily or equivalent). Intranasal and/or
inhaled corticosteroid use is permitted.

- Any unresolved CTCAE grade >2 toxicity from previous anti-cancer therapy. Patients
with irreversible toxicity that is not reasonably expected to be exacerbated by study
therapy (eg, hearing loss)may be enrolled after discussion with the principal
investigators.

- History of allogeneic organ transplant or autoimmune disease

- Active malignancy, other than NSCLC, for which systemic therapy is indicated. History
of adequately treated local basal cell or squamous cell carcinoma of the skin,
cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer
without known metastatic disease and with no requirement for therapy asides from
hormonal therapy, adequately treated stage 1 or 2 cancer currently in complete
remission, or any other cancer that has been in complete remission for >= 5 years is
permitted.

- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,
or psychiatric illness/social situation that would limit compliance with study
requirements as judged by the treating physicians

- The following laboratory results, within 10 days of first study drug administration:

- Hemoglobin . 9.0 g/dL, Absolute neutrophil count . 1.5 x 109/L, Platelet count .
100 x 109/L

- Serum creatinine . 1.5 x ULN and creatinine clearance (by Cockcroft-Gault
formula) < 60 mL/min

- Women of child bearing potential: positive pregnancy test (serum)