Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer

Purpose Belagenpumatucel-L is a nonviral gene-based allogeneic tumor cell vaccine that demonstrates enhancement of tumor antigen recognition as a result of transforming growth factor beta-2 inhibition. Patients and Methods We performed a randomized, dose-variable, phase II trial involving stages II, IIIA, IIIB, and IV non-small-cell lung cancer patients. Each patient received one of three doses (1.25, 2.5, or 5.0 x 10(7) cells/injection) of belagenpumatucel-L on a monthly or every other month schedule to a maximum of 16 injections. Immune function, safety, and anticancer activity were monitored. Results Seventy-five patients ( two stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients) received a total of 550 vaccinations. No significant adverse events were observed. A dose-related survival difference was demonstrated in patients who received >= 2.5 x 10(7) cells/injection ( P =.0069). Focusing on the 61 late-stage ( IIIB and IV) assessable patients, a 15% partial response rate was achieved. The estimated probabilities of surviving 1 and 2 years were 68% and 52%, respectively for the higher dose groups combined and 39% and 20%, respectively, for the low-dose group. Immune function was explored in the 61 advanced-stage ( IIIB and IV) patients. Increased cytokine production ( at week 12 compared with patients with progressive disease) was observed among clinical responders ( interferon gamma, P =.006; interleukin [IL] - 6, P =.004; IL-4, P =.007), who also displayed an elevated antibody-mediated response to vaccine HLAs ( P =.014). Furthermore, positive enzyme-linked immunospot reactions to belagenpumatucel-L showed a correlation trend ( P =.086) with clinical responsiveness in patients achieving stable disease or better. Conclusion Belagenpumatucel-L is well tolerated, and the survival advantage justifies further phase III evaluation.