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Ref Type Journal Article
PMID (26843484)
Authors Wheeler LA, Manzanera AG, Bell SD, Cavaliere R, McGregor JM, Grecula JC, Newton HB, Lo SS, Badie B, Portnow J, Teh BS, Trask TW, Baskin DS, New PZ, Aguilar LK, Aguilar-Cordova E, Chiocca EA
Title Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma.
Journal Neuro-oncology
Vol 18
Issue 8
Date 2016 Aug
URL
Abstract Text 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.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.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.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.ClinicalTrials.gov NCT00589875.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AdV-tk AdV-tk 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
AdV-tk Aglatimagene besadenovec|GliAtak|ProstAtak|Virafir Aglatimagene besadenovec (AdV-tk) is an engineered adenoviral vector expressing the herpes simplex virus thymidine kinase that sensitizes tumor cells to therapy with acyclic guanosine analogues (PMID: 26843484, PMID: 30883662).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown malignant glioma not applicable AdV-tk + Valacyclovir Phase II Actionable In a Phase II trial, addition of AdV-tk and Valacyclovir to standard of care improved meidan overall survival (17.1 vs 13.5 months) compared to standard of care alone in patients with malignant glioma (PMID: 26843484). 26843484