Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer

Inclusion Criteria

- Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Squamous
cell (epidermoid), adenocarcinoma, bronchoalveolar carcinoma and large cell
anaplastic lung carcinoma histologies are eligible. Mixed histologies of NSCLC (i.e.,
adenosquamous) are eligible. Mixed NSCLC/small cell lung carcinoma (SCLC), and
variant large and small cell lung cancer are NOT eligible for this study.

- Measurable disease as defined by RECIST 1.1 Criteria.

- At least one but no more than three prior lines of therapy in the advanced stage are
allowed. One prior line of therapy must be platinum doublet chemotherapy.

- At least 18 years of age.

- ECOG performance status ≤ 1

- Normal bone marrow and organ function as defined below:

- Marrow: Hemoglobin ≥10.0 gm/dL, absolute granulocyte count (AGC) ≥1,000/mm3
platelets ≥100,000/mm3, absolute lymphocyte count ≥1000/mm3.

- Hepatic: Serum/plasma total bilirubin ≤1.5 x upper limit of normal (ULN) with
the exception of <2.9 mg/dL for patients with Gilbert's disease, ALT (SGPT) and
AST (SGOT) ≤2.5 x ULN.

- Renal: Serum/plasma creatinine (sCr) ≤1.5 x upper limit of normal, or creatinine
clearance (Ccr) ≥50 mL/min.

- Serum/plasma albumin > 3.0 gm/dL

- Sexually active women of child-bearing potential must agree to use two forms of
contraception prior to study entry and for the duration of study participation. A
pregnancy test is required prior to study enrollment and monthly while on treatment
with indoximod for all women of child- bearing potential. Also men should be
discouraged from fathering children while on treatment.

- Ability to understand and willingness to sign an IRB approved written informed
consent document.

Exclusion Criteria

- More than three lines of prior therapy.

- Previous use of indoximod or tergenpumatucel-L immunotherapy.

- A history of other malignancy, unless treated with curative intent, and no evidence
of disease for at least 2 years.

- Current therapy with any other investigational agents.

- Untreated CNS disease, metastases or carcinomatous meningitis. Patients with CNS
metastases must be at least 2 weeks status post prior therapy to the brain and be off
all steroids without progressing CNS disease or symptoms.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to indoximod, docetaxel, or other agents used in the study.

- Current use of immunosuppressive drugs or use of corticosteroids, except for inhaler,
topical corticosteroids, or dexamethasone in the premedication for docetaxel.

- Other malignancy within three years, unless the probability of recurrence of the
prior malignancy is <5%. Patient's curatively treated for squamous cell carcinoma and
basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or
patients with a history of malignant tumor in the past that have been disease free
for at least five years are also eligible for this study.

- History of organ transplant.

- Any of the following within 6 months prior to study drug administration:

- Myocardial infarction

- Severe/unstable angina

- Coronary/peripheral artery bypass graft

- Symptomatic congestive heart failure

- Cerebrovascular accident or transient ischemic attack

- Pulmonary embolism

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, uncontrolled ongoing cardiac dysrhythmias of ≥ grade 2, or psychiatric
illness/social situations that would limit compliance with study requirements

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.

- Known HIV-positivity on combination antiretroviral therapy because of the unknown
potential for pharmacokinetic interactions with indoximod, or docetaxel. In addition,
these patients are at increased risk of lethal infections when treated with marrow
suppressive therapy.

- Active autoimmune disease requiring systemic therapy. Patients with a history of
autoimmune disease must be counselled regarding the unknown potential of exacerbating
or reactivating previous or dormant autoimmunity during the consent process.