Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma

Lee A. Wheeler, Andrea G. Manzanera, Susan D. Bell, Robert Cavaliere, John M. McGregor, John C. Grecula, Herbert B. Newton, Simon S. Lo, Behnam Badie, Jana Portnow, Bin S. Teh, Todd W. Trask, David S. Baskin, Pamela Z. New, Laura K. Aguilar, Estuardo Aguilar-Cordova, E. Antonio Chiocca

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


Background Despite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This Phase II, prospective, matched controlled, multicenter trial was conducted to assess the safety and efficacy of aglatimagene besadenovec (AdV-tk) plus valacyclovir (gene-mediated cytotoxic immunotherapy [GMCI]) in combination with SOC for newly diagnosed malignant glioma patients. Methods Treatment cohort patients received SOC + GMCI and were enrolled at 4 institutions from 2006 to 2010. The preplanned, matched-control cohort included all concurrent patients meeting protocol criteria and SOC at a fifth institution. AdV-tk was administered at surgery followed by SOC radiation and temozolomide. Subset analyses were preplanned, based on prognostic factors: pathological diagnosis (glioblastoma vs others) and extent of resection. Results Forty-eight patients completed SOC + GMCI, and 134 met control cohort criteria. Median overall survival (OS) was 17.1 months for GMCI + SOC versus 13.5 months for SOC alone (P =. 0417). Survival at 1, 2, and 3 years was 67%, 35%, and 19% versus 57%, 22%, and 8%, respectively. The greatest benefit was observed in gross total resection patients: median OS of 25 versus 16.9 months (P =. 0492); 1, 2, and 3-year survival of 90%, 53%, and 32% versus 64%, 28% and 6%, respectively. There were no dose-limiting toxicities; fever, fatigue, and headache were the most common GMCI-related symptoms. Conclusions GMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival outcomes were most notably improved in patients with minimal residual disease after gross total resection. These data should help guide future immunotherapy studies and strongly support further evaluation of GMCI for malignant gliomas. Clinical trial registry NCT00589875.

Original languageEnglish (US)
Pages (from-to)1137-1145
Number of pages9
Issue number8
StatePublished - Aug 1 2016


  • Gene therapy
  • Glioblastoma
  • Immuno-oncology
  • Immunotherapy
  • Malignant glioma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research


Dive into the research topics of 'Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma'. Together they form a unique fingerprint.

Cite this