1104. Phase II Study of Lucanix™ a Transforming Growth Factor β2 (TGF-β2) Antisense Gene Modified Allogeneic Tumor Cell Vaccine in Non Small Cell Lung Cancer (NSCLC)

Abstract

Lucanix™ is a non-viral gene based allogeneic tumor cell vaccine. Preclinical studies demonstrate enhancement of tumor antigen recognition as a result of TGF-β2 inhibition.We performed a randomized dose variable phase II trial involving stage II, IIIA, IIIB and IV NSCLC. Each patient received one of 3 doses (1.25, 2.5, 5.0x107 cells/injection) of Lucanix™ on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety and anticancer activity were monitored. Seventy five patients (2 stage II, 12 IIIA, 15 IIIB, 46 IV), received a total of 550 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=0.0069). Focusing on the sixty- one late stage (IIIb/IV) evaluable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% (95% CI: 55%, 80%) and 52% (95% CI: 35%, 68%) for the two higher-dose groups combined and was 39% (95% CI: 22%, 66%) and 20% (95% CI: 4%, 36%) for the low dose group. Immune function was explored in the 61 advanced stage (IIIB/IV) patients. 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 compared to those with progressive disease. In conclusion, Lucanix™ 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. Lucanix™ is a non-viral gene based allogeneic tumor cell vaccine. Preclinical studies demonstrate enhancement of tumor antigen recognition as a result of TGF-β2 inhibition. We performed a randomized dose variable phase II trial involving stage II, IIIA, IIIB and IV NSCLC. Each patient received one of 3 doses (1.25, 2.5, 5.0x107 cells/injection) of Lucanix™ on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety and anticancer activity were monitored. Seventy five patients (2 stage II, 12 IIIA, 15 IIIB, 46 IV), received a total of 550 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=0.0069). Focusing on the sixty- one late stage (IIIb/IV) evaluable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% (95% CI: 55%, 80%) and 52% (95% CI: 35%, 68%) for the two higher-dose groups combined and was 39% (95% CI: 22%, 66%) and 20% (95% CI: 4%, 36%) for the low dose group. Immune function was explored in the 61 advanced stage (IIIB/IV) patients. 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 compared to those with progressive disease. In conclusion, Lucanix™ 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.