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.

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.

• Authors: John Nemunaitis, Robert O Dillman, Paul O Schwarzenberger, Neil Senzer, Casey Cunningham, Jodi Cutler, Alex Tong, Padmasini Kumar, Beena Pappen, Cody Hamilton, Edward DeVol, Phillip B Maples, Lily Liu, Terry Chamberlin, Daniel L Shawler, Habib Fakhrai
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 29 Pg. 4721-30 (Oct 10 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16966690 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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