Phase II study of a TGF-β2 antisense gene modified allogeneic tumor cell vaccine (Lucanix) in advanced NSCLC

Abstract

7018 Background: Lucanix (L) is a non-viral gene based allogeneic tumor cell vaccine which demonstrates enhancement of tumor antigen recognition as a result of Transforming Growth Factor (TGF-β2) inhibition. Methods: We performed a randomized dose variable phase II trial involving stage IIIB/IV non small cell lung cancer (NSCLC). Each patient received one of 3 doses (1.25, 2.5, 5.0x107 cells/injection) of L, given intradermally, to a maximum of 16 injections either monthly or every other month. Immune function, safety and anticancer activity were monitored. Results: Sixty-one patients (15 IIIB/ 46 IV; 51/61 (84%) ≥ prior cytotoxic therapy), received a total of 417 vaccinations. No significant (≥ grade 3) adverse events probably or definitely associated with administration of the vaccine were observed. A dose-related survival difference was demonstrated in patients who received ≥ 2.5 × 107 cells/injection versus those who received <2.5 × 107 cells/injection (p=0.0151). The percent of patients surviving 1 and 2 years was 61% and 52% for the high dose group and 40% and 13% for the low dose group. Fifteen percent of patients achieved a partial response. Cytokine production (IFN-γ, p=0.006; IL-6, p=0.004; IL4, p=0.007) was induced, antibody mediated response to vaccine HLA antigen was observed (p=0.014) and cell mediated response showed a correlation trend (p=0.086) in patients achieving stable disease or partial response (15%) compared to those with progressive disease. Conclusions: In conclusion, L is safe and well tolerated. A survival advantage is suggested in patients who receive ≥ 2.5x107 cells/injection thereby supporting the justification for further phase III evaluation. Phase III investigation is recommended. [Table: see text]