DNP-Modified Autologous Tumor Cell Vaccine for Resectable Non-Small Cell Lung Cancer

Study Objectives: To study the toxicity, safety and delayed-type hypersensitivity (DTH) responses of DNP-modified autologous tumor cell vaccine (L-Vax) in patients with resectable NSCLC:

To determine the tolerability and toxicity of L-Vax
To determine whether L-Vax induces a DTH response to autologous, DNP-modified NSCLC cells of similar magnitude to responses observed with melanoma
Determine whether L-Vax induces a DTH response to autologous unmodified NSCLC cells
To determine whether the DTH responses to autologous, unmodified NSCLC cells that have been fixed with ethanol correlate with DTH responses to autologous, unmodified NSCLC cells that are not fixed

Study Population: Patients with resectable NSCLC whose therapeutic tumor surgery provides a mass, which yields adequate tumor, cells for vaccine preparation and DTH testing

Study Design: A Phase I/IIa double-blind, three-dose, single center study

Investigational Product: L-Vax: DNP-modified autologous NSCLC cell vaccine

Dosage Form: Cell suspension

Route of Administration: Intradermal

Dosage and Treatment Schedule: Prior to vaccine administration, patients will be tested for DTH to autologous NSCLC cells that have been: DNP-modified, or unmodified and irradiated, or unmodified and irradiated and fixed with ethanol (if sufficient cells available) Three doses of vaccine will be tested: 5 x 105, 2.5 x 106, or 5 x 106 DNP-modified autologous NSCLC cells. An initial dose of DNP-modified autologous NSCLC cells* without Bacillus of Calmette and Guérin (BCG) followed by cyclophosphamide (CY) then weekly doses of DNP-modified autologous NSCLC tumor cells mixed with BCG for 6 weeks, and completed with one dose of DNP-modified autologous NSCLC tumor cells mixed with BCG as a 6-month booster, if adequate number of cells available.

count determined prior to aliquoting for cryopreservation

Endpoints: Treatment-emergent and related adverse events, serious adverse events, and Grade 3 and 4 laboratory abnormalities for safety assessments

Other Parameters: · DTH skin reactions for assessing the induction of immune responses to DNP-modified and unmodified autologous NSCLC tumor cells· Survival· Exploratory analysis of in vitro studies of peripheral blood lymphocytes obtained from study subjects

Duration of Treatment: Up to 9 months

Duration of Subject Participation in Study: Three months from the patient's last vaccine

Duration of Follow-up: Survival information and disease status will be collected via phone or visit on a quarterly basis for each patient beginning 30 days after the last scheduled visit until the last patient has been followed for three months from his/her last vaccine

Number of Subjects Required to Meet Protocol Objectives: Up to 42 evaluable subjects

Number of Study Centers: Three

Number of Individual Blood Draws: 15 draws over nine months

Volume of Blood Drawn: 13 Draws of 30 mL/draw (total 360 mL) and two draws of 50mL in heparinized tubes