Originally published as JCO Early Release 10.1200/JCO.2005.05.5335 on September 11 2006

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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

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

From the Mary Crowley Medical Research Center/Texas Oncology Professional Association; Baylor Sammons Cancer Center, Baylor University Medical Center; Murex Pharmaceutical Inc; Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, TX; Hoag Cancer Center, Newport Beach; NovaRx Corporation, San Diego, CA; and Louisiana State University, New Orleans, LA

Address reprint requests to John Nemunaitis, MD, 1717 Main St, 60th Floor, Dallas, TX 75201; e-mail: jnemunaitis{at}mcmrc.com

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 10⁷ 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 10⁷ 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.

published online ahead of print at www.jco.org on September 11, 2006.

Supported in part by Small Business Innovative Research Grant No. 1 R44 CA96025 (H.F.).

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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