Effect of Talactoferrin in Adults With Non-Small Cell Lung Cancer

Background:

Patients with locally advanced or metastatic NSCLC have a very poor prognosis even with
surgery, chemotherapy, and radiation treatments.

Patients who respond to 1st line chemotherapy invariably develop disease progression, and
their median survival is between 6-8 months.

Talactoferrin alfa (TLF) is a recombinant human lactoferrin.

TLF displays anti-infective (against bacteria, viruses, protozoa and fungi) and
anti-inflammatory properties, anti-tumor activity and anti-asthma properties.

Preclinical studies have demonstrated an increase in cytokines that stimulate both innate and
adaptive immunity, as well as increasing the numbers of NK-T cells and CD8+ T-lymphocytes
found in Peyer s Patches.

Previous studies in NSCLC have demonstrated safety and evidence of clinical activity.

Objectives:

Primary: To evaluate the effects of administration of talactoferrin to patients with advanced
non-small cell lung cancer on the quantitative and functional changes in CD4, CD8, NK, and
Treg populations in peripheral blood mononuclear cells (PBMC) and on the levels of cytokines
and chemokines in serum.

Secondary: To evaluate clinical response to talactoferrin. To evaluate the safety of
talactoferrin.

Eligibility:

Patients with cytologically or histologically confirmed progressive, recurrent, or refractory
stage IIIb or IV NSCLC.

Patients must be HLA-A2 positive.

Design:

Single-arm pilot study

Ten patients will be enrolled to receive daily oral talactoferrin (1.5 g/ bid) for up to 12
weeks.

Patients who benefit from treatment will be able to continue on a 12 weeks on 2 weeks off
schedule until progression.

Evaluation will be performed every 3 weeks with CT chest, abdomen, and pelvis at baseline,
week 6, and week 12.

Immunologic studies (including apheresis) will be performed at baseline, week 6, and week 12.

- INCLUSION CRITERIA:

Age greater than or equal to 18 years

Histologically or cytologically confirmed progressive, recurrent, or refractory stage IIIB
or IV NSCLC; confirmation of pathologic diagnosis to be conducted at the NCI Laboratory of
Pathology

Patients may not be eligible for other curative intent treatment (e.g., surgical
resection). For the purpose of eligibility for this trial, the above-cited disease states
are defined as follows:

- Progressive NSCLC defined as increasing measurable disease, or the appearance of new
measurable disease by RECIST criteria.

- Recurrent NSCLC defined as the reappearance of measurable disease or the appearance of
new measurable disease by RECIST criteria after prior successful treatment or complete
response.

- Refractory NSCLC defined as achieving less than a complete response and having
residual measurable disease by RECIST criteria after prior treatment with
chemotherapy, targeted or small molecules, monoclonal antibodies, or any combination
of these.

- Patients may enroll who are not candidates for, or who have documented refusal to
receive standard therapy (e.g., chemotherapy) for their disease.

HLA-A2 allele

Patient must have evaluable or measurable disease

Total bilirubin less than or equal to 1.5 mg/dL (OR in patients with Gilbert s syndrome, a
total bilirubin less than or equal to 3.0)

Creatinine less than 1.5 times Upper Limit of Normal (ULN) if greater than 1.5 times ULN,
creatinine clearance on a 24 hour urine collection of greater than 60 mL/min.

AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times the upper limit of normal (ULN);
in case of liver metastases less than or equal to 5 x ULN

Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2

Able to understand and give informed consent

Recovered completely from any reversible toxicity associated with recent therapy. Typically
this is 3-4 weeks for patients who most recently received cytotoxic therapy except for the
nitrosoureas and mitomycin C for which 6 weeks is needed for recovery.

Hematological eligibility parameters (within 16 days of starting therapy):

- Granulocyte count greater than or equal to 1,500/mm(3)

- Platelet count greater than or equal to 75,000/mm(3)

- Hgb greater than or equal to 9 Gm/dL

EXCLUSION CRITERIA:

Presence of brain metastases, unless the patient received brain irradiation at least 4
weeks prior to enrollment, and is stable, asymptomatic, and off steroids for at least 4
weeks prior to registration

History of allergic reactions to compounds of similar chemical or biologic composition to
Talactoferrin. At this point, no specific compounds have been identified.

History of other malignancies except: (i) adequately treated basal or squamous cell
carcinoma of the skin; (ii) curatively treated, a) in situ carcinoma of the uterine cervix,
b) prostate cancer, or c) superficial bladder cancer; or (iii) other curatively treated
solid tumor with no evidence of disease for greater than or equal to 5 years

Uncontrolled ischemic heart disease, or uncontrolled symptomatic congestive heart failure

Serious active infection

Psychiatric illness/ social situations that would limit study compliance

Other uncontrolled serious chronic disease or conditions that in the investigator s opinion
could render compliance or follow-up in the protocol problematic

Concurrent radiotherapy or radiotherapy within 4 weeks prior to enrollment or previous
radiotherapy to the target lesion sites (the sites that are to be followed for
determination of a response)

Concurrent use of topical steroids (including steroid eye drops) or systemic steroids.
Nasal or inhaled steroid use is permitted.

HIV positive

Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)

History of opportunistic infections

Hepatitis B surface antigen positive or hepatitis C positive

Receipt of any investigational medication within 4 weeks prior to enrollment.

Pregnant or lactating patients, or fertile female patients with a positive pregnancy test
(serum beta-human chorionic gonadotropin [beta-hCG] at screening and at baseline), or
fertile female patients unwilling to use adequate contraception (including condom use,
birth control pills, or IUD) during treatment and 30 days after completion of treatment

Sexually active male patients unwilling to practice contraception (condom use) while
participating on the study and up to 30 days after completion of treatment

Legal incapacity or limited legal capacity, unless authorization is granted by a legal
guardian