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

J Clin Oncol. 2006 Oct 10;24(29):4721-30. doi: 10.1200/JCO.2005.05.5335. Epub 2006 Sep 11.

Abstract

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 > or = 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Formation / drug effects
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Oligonucleotides, Antisense / adverse effects
  • Oligonucleotides, Antisense / immunology
  • Oligonucleotides, Antisense / therapeutic use*
  • Survival Analysis
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta2
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Oligonucleotides, Antisense
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • belagenpumatucel L
  • Interferon-gamma