Abstract 5367: Long-term survival in a phase II atudy of belagenpumatucel-L (TGF-β antisense modified tumor cell vaccine) in non-small cell lung cancer (NSCLC).

Abstract

Abstract Background: Cancer therapeutics vaccines continue to be investigated in a variety of solid malignancies. Belagenpumatucel-L (Lucanix®), a therapeutic vaccine comprised of 4 TGF-β2 antisense gene-modified allogeneic NSCLC cell lines. Phase II trial finished its enrollment in March of 2004 and was published in 2006. We now report an updated survival analysis with over 5 years of follow up. Methods: Three arms, open label clinical trial enrolled seventy-five subjects. 2 stage II, 12 stage IIIA, 15 stage IIIB, and 46 stage IV patients were randomized into three dose cohorts of 1.25, 2.5, or 5 107 cells/injection. Several cellular (ELISPOT and cytoplasmic cytokine expression) and humoral (antibody ELISA) immunity assays were also performed and correlated with survival. Results: Median follow up for all patients was 14.5 months and for patients with stable disease 44 months. Median survival for all subjects was 14.5 months and one-year, two-years and five-year survival were respectively 55%, 35% and 20%. Stages IIIB/IV subjects enrolled into cohorts 2 and 3 (N=40) had a median survival of 15.9 months and one-year, two-year and five-year survivals were respectively 61%, 41% and 18%. For stage IIIB/IV patients with non progressive disease following frontline chemotherapy, median survival was 44.4 months and five-year survival was 50%. For subjects who progressed following frontline chemotherapy, median survival was 14.1 months and five-year survival was 9.1%. Subjects who demonstrated an increase in both cellular and humoral immune reactivity following treatment had a significant survival advantage over subjects who showed an increase in only one measure of immunity with a median survival of 32.5 months vs. 11.6 months (p = 0.015). Conclusion: Long term follow up of a phase II clinical trial confirmed encouraging survival for patients with stage IIIB/IV disease. Based on these data, we have instituted an international, randomized, pivotal Phase III trial to evaluate the efficacy of belagenpumatucel-L in a maintenance setting in stage III/IV NSCLC patients who have stable disease or better following frontline chemotherapy. The trial is designed to enroll 506 patients and is powered to measure a 3.5 month survival difference. There are two planned interim analyses. To date, 285 patients have been enrolled in 8 countries. Confirmation of the phase II data in a randomized, phase III setting would provide an important improvement for the treatment of non-small cell lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5367. doi:1538-7445.AM2012-5367