631. Phase 1/2 Trial of Autologous Tumor Mixed with an Allogeneic GVAX® Immunotherapy in Advanced Stage Non-Small Cell Lung Cancer

Abstract

We have previously demonstrated activity with immunotherapy composed of autologous tumor cells genetically modified to secrete GM-CSF (GVAX®) in advanced stage NSCLC1. In an effort to remove the requirement and variability associated with genetic transduction of individual tumors we developed a “bystander” GVAX® platform composed of autologous tumor cells mixed with an allogeneic GM- CSF secreting cell line. We conducted a phase I/II trial of this immunotherapy (3 to 12 biweekly injections) in advanced stage NSCLC. Tumors were harvested from 86 patients, tumor cell processing was successful in 76, and 49 received study treatment. The most common toxicity was local injection site reactions. Serum GM-CSF pharmacokinetics were consistent with secretion of GM- CSF from the injected cells for up to 4 days with associated transient leukocytosis confirming GM-CSF bioactivity. Evidence of treatment-induced immune activation was demonstrated; however, objective tumor responses were not seen. Compared with autologous GVAX® immunotherapy for lung cancer prepared by transduction of individual tumors with an adenoviral GM-CSF vector, GM-CSF secretion was approximately 25-fold higher with the bystander GVAX® product used in this trial. However, the frequency of injection site reactions, tumor response, time to disease progression, and survival were all less favorable in the current study in comparison to prior results. Follow-up results will be presented. 1. Nemunaitis J, Sterman D, Jablons D, et al. Granulocyte- macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 2004;96(4):326–31.