. Neuro Oncol. 2016 Feb 2. pii: now002. [Epub ahead of print]

Phase 2 multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.

Wheeler LA1, Manzanera AG1, Bell SD1, Cavaliere R1, McGregor JM1, Grecula JC1, Newton HB1, Lo SS1, Badie B1, Portnow J1, Teh BS1, Trask TW1, Baskin DS1, New PZ1, Aguilar LK1, Aguilar-Cordova E1, Chiocca EA1.

 

Author information:

1Brigham and Women's Hospital/Harvard Medical School, Massachusetts (L.A.W., E.A.C.); Advantagene, Inc., Auburndale, Massachusetts (A.G.M., L.K.A., E.A.-C.); Ohio State University, Columbus, Ohio (S.D.B., R.C., J.M.M., J.C.G., H.B.N.); University Hospitals Seidman Cancer Center/ Case Western Reserve University, Cleveland, Ohio (S.S.L.); City of Hope, Duarte, California (B.B., J.B.); Houston Methodist Hospital, Houston, Texas (B.S.T., T.W.T., D.S.B., P.Z.N.).

 

Abstract

BACKGROUND:

 

Despite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This phase 2, 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:

 

ClinicalTrials.gov NCT00589875.